Stem cellFrom Wikipedia, the free encyclopedia

Stem cell

Mouse embryonic stem cells with fluorescent marker

Human embryonic stem cell colony on mouse embryonic fibroblast feeder

layer

Latin cellula precursoria

Code TH H2.00.01.0.00001

This article is about the cell type. For the medical therapy, see Stem Cell Treatments.

Stem cells are biological cells found in all multicellular organisms, that can divide (throughmitosis) and differentiate into diverse specialized cell types and can self-renew to produce more stem cells. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells (these are called pluripotent cells), but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three sources of autologous adult stem cells: 1) Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest), 2) Adipose tissue (lipid cells), which requires extraction by liposuction, and 3) Blood, which requires extraction through pheresis, wherein blood is drawn from the donor (similar to a blood donation), passed through a machine that extracts the stem cells and returns other portions of the blood to the donor. Stem cells can also be taken from umbilical cord blood. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.

Highly plastic adult stem cells are routinely used in medical therapies, for example bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves through cell culture. Embryonic cell lines and autologousembryonic stem cells generated through therapeutic cloning have also been proposed as promising candidates for future therapies.[1] Research into

stem cells grew out of findings byErnest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

Contents

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1 Propertieso 1.1 Self-renewalo 1.2 Potency definitionso 1.3 Identification

2 Embryonic3 Fetal4 Adult5 Amniotic6 Induced pluripotent7 Lineage8 Treatments9 Research patents10 Key research events11 See also12 References13 External links

Properties

The classical definition of a stem cell requires that it possess two properties:

Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.

Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent orpluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it

is said that stem cell function is regulated in a feed back mechanism.

Self-renewal

Two mechanisms to ensure that a stem cell population is maintained exist:

1. Obligatory asymmetric replication : a stem cell divides into one father cell that is identical to the original stem cell, and another daughter cell that is differentiated

2. Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original.

Potency definitions

Pluripotent, embryonic stem cells originate as inner cell mass (ICM) cells within a blastocyst. These stem cells can become any tissue in the body, excluding a placenta. Only cells from an earlier

stage of the embryo, known as the morula, are totipotent, able to become all tissues in the body and the extraembryonic placenta.

Human embryonic stem cellsA: Cell colonies that are not yet differentiated.B: Nerve cell

Main article: Cell potency

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]

Totipotent  (a.k.a. omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.[4] These cells are produced from the fusion of an egg and sperm cell. Cells

produced by the first few divisions of the fertilized egg are also totipotent.[5]

Pluripotent  stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[4] i.e. cells derived from any of the three germ layers.[6]

Multipotent  stem cells can differentiate into a number of cells, but only those of a closely related family of cells.[4]

Oligopotent  stem cells can differentiate into only a few cells, such as lymphoid or myeloid stem cells.[4]

Unipotent  cells can produce only one cell type, their own,[4] but have the property of self-renewal, which distinguishes them from non-stem cells (e.g., muscle stem cells).

Identification

The practical definition of a stem cell is the functional definition—a cell that has the potential to regenerate tissue over a lifetime. For example, the defining test for a bone marrow or hematopoietic stem cell (HSC) is the ability to transplant one cell and save an individual without HSCs. In this case, a stem cell must be able to produce new blood cells and immune cells over a long term, demonstrating potency. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[7][8]Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.

Embryonic

Main article: Embryonic stem cell

Embryonic stem (ES) cell lines are cultures of cells derived from the epiblast tissue of theinner cell mass (ICM) of a blastocyst or earlier morula stage embryos.[9] A blastocyst is an early stage embryo—approximately four to five days old in humans and consisting of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta. The endoderm is composed of the entire gut tube and the lungs, the ectoderm gives rise to the nervous system and skin, and the mesoderm gives rise to muscle, bone, blood—in essence, everything else that connects the endoderm to the ectoderm.

Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF).[10]Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[11] Without optimal culture conditions or genetic manipulation,[12] embryonic stem cells will rapidly differentiate.

A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[13] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The

molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[14]

There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[15] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal injury victims. On November 14, 2011 the company conducting the trial announced that it will discontinue further development of its stem cell programs.[16] ES cells, being pluripotent cells, require specific signals for correct differentiation—if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[17] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

Fetal

The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[18]

Adult

Main article: Adult stem cell

Stem cell division and differentiation. A: stem cell; B: progenitor cell; C: differentiated cell; 1: symmetric stem cell division; 2: asymmetric stem cell division; 3: progenitor division; 4: terminal differentiation

Also known as somatic (from Greek Σωματικóς, "of the body") stem cells and germline (giving rise to gametes) stem cells, they can be found in children, as well as adults.[19]

Pluripotent adult stem cells are rare and generally small in number but can be found in a number of tissues including umbilical cord blood.[20] A great deal of adult stem cell research to date has had the aim of characterizing the capacity of the cells to divide or self-renew indefinitely and their differentiation potential.[21]In mice, pluripotent stem cells are directly generated from adult fibroblast cultures. Unfortunately, many mice do not live long with stem cell organs.[22]

Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[23][24]

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[25] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[26]

The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[27]

An extremely rich source for adult mesenchymal stem cells is the developing tooth bud of the mandibular third molar.[28] The stem cells eventually form enamel (ectoderm), dentin, periodontal ligament, blood vessels, dental pulp, nervous tissues, and a minimum of 29 different end organs. Because of extreme ease in collection at 8–10 years of age before calcification and minimal to no morbidity, these will probably constitute a major source of cells for personal banking, research and current or future therapies. These stem cells have been shown capable of producing hepatocytes.[citation needed]

Amniotic

Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[29] All over the world, universities and research institutes are studying amniotic fluid to discover all the qualities of amniotic stem cells, and scientists such as Anthony Atala [30] [31]  and Giuseppe Simoni [32][33][34] have discovered important results.

Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholicteaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[35]

It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank [36][37] was opened in 2009 in Medford, MA, by Biocell Center Corporation [38]

[39][40] and collaborates with various hospitals and universities all over the world.[41]

Induced pluripotent

Main article: Induced pluripotent stem cell

These are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[42][43][44] Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4[42] in their experiments on cells from human faces. Junying Yu, James Thomson, and their colleagues at the University of Wisconsin–Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28,[42] and carried out their experiments using cells from human foreskin.

As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[45]

Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells.[46]

Lineage

Main article: Stem cell line

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminallydifferentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[47]

An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegicand adherens junctions that prevent germarium stem cells from differentiating.[48][49]

Main article: Induced Pluripotent Stem Cell

The signals that lead to reprogramming of cells to an embryonic-like state are also being investigated. These signal pathways include severaltranscription factors including the oncogene c-Myc. Initial studies indicate that transformation of mice cells with a combination of these anti-differentiation signals can reverse differentiation and may allow adult cells to become pluripotent.[22] However, the need to transform these cells with an oncogene may prevent the use of this approach in therapy.

Challenging the terminal nature of cellular differentiation and the integrity of lineage commitment, it was recently determined that the somatic expression of combined transcription factors can directly induce other defined somatic cell fates; researchers

identified three neural-lineage-specific transcription factors that could directly convert mouse fibroblasts (skin cells) into fully functional neurons. This "induced neurons" (iN) cell research inspires the researchers to induce other cell types implies that all cells are totipotent: with the proper tools, all cells may form all kinds of tissue.[50]

Treatments

Main article: Stem cell treatments

Diseases and conditions where stem cell treatment is promising or emerging.[51] Bone marrow transplantation is, as of 2009, the only established use of stem cells.

Medical researchers believe that stem cell therapy has the potential to dramatically change the treatment of human disease. A number of adult stem cell therapies already exist, particularly bone marrow transplants that are used to treat leukemia.[52] In the future, medical researchers anticipate being able to use technologies derived from stem cell research to treat a wider variety of diseases including cancer, Parkinson's disease, spinal cord injuries,Amyotrophic lateral sclerosis, multiple sclerosis, and muscle damage, amongst a number of other impairments and conditions.[53][54] However, there

still exists a great deal of social and scientific uncertainty surrounding stem cell research, which could possibly be overcome through public debate and future research, and further education of the public.

One concern of treatment is the risk that transplanted stem cells could form tumors and become cancerous if cell division continues uncontrollably.[55]

Stem cells are widely studied, for their potential therapeutic use and for their inherent interest.[56]

Supporters of embryonic stem cell research argue that such research should be pursued because the resultant treatments could have significant medical potential. It has been proposed that surplus embryos created for in vitro fertilization could be donated with consent and used for the research.

The recent development of iPS cells has been called a bypass of the legal controversy. Laws limiting the destruction of human embryos have been credited for being the reason for development of iPS cells, but it is still not completely clear whether hiPS cells are equivalent to hES cells. Recent work demonstrates hotspots of aberrant epigenomic reprogramming in hiPS cells (Lister, R., et al., 2011).

Research patents

The patents covering a lot of work on human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF). WARF does not charge academics to study human stem cells but does charge commercial users. WARF sold Geron Corp. exclusive rights to work on human stem cells but later sued Geron Corp. to recover some of the previously sold rights. The two sides agreed that Geron Corp. would keep the rights to only three cell types. In 2001, WARF came under public pressure to widen access to human stem-cell technology.[57]

A request for reviewing the WARF patents 5,843,780; 6,200,806; 7,029,913 US Patent and Trademark Office were filed by non-profit patent-watchdogs The Foundation for Taxpayer & Consumer Rights, and the Public Patent Foundation as well as molecular biologist Jeanne Loring of the Burnham Institute. According to them, two of the patents granted to WARF are invalid because they cover a technique published in 1993 for which a patent had already been granted to an Australian researcher. Another part of the challenge states that these techniques, developed by James A. Thomson, are rendered obvious by a 1990 paper and two textbooks. Based on this challenge, patent 7,029,913 was rejected in 2010. The two remaining hES WARF patents are due to expire in 2015.

The outcome of this legal challenge is particularly relevant to the Geron Corp. as it can only license patents that are upheld.[58]

Key research events

1908: The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.

1960s: Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; like André Gernez, their reports contradict Cajal's "no new neurons" dogma and are largely ignored.

1963: McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.

1968: Bone marrow transplant between two siblings successfully treats SCID.

1978: Haematopoietic stem cells are discovered in human cord blood.

1981: Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman,

and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".

1992: Neural stem cells are cultured in vitro as neurospheres. 1997: Leukemia is shown to originate from a haematopoietic

stem cell, the first direct evidence for cancer stem cells. 1998: James Thomson and coworkers derive the first human

embryonic stem cell line at the University of Wisconsin–Madison.[59]

1998: John Gearhart (Johns Hopkins University) extracted germ cells from fetal gonadal tissue (primordial germ cells) before developing pluripotent stem cell lines from the original extract.

2000s: Several reports of adult stem cell plasticity are published.

2001: Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[60]

2003: Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[61]

2004–2005: Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised humanoocytes. The lines were later shown to be fabricated.

2005: Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.

2005: Researchers at UC Irvine's Reeve-Irvine Research Center are able to partially restore the ability of rats with paralyzed spines to walk through the injection of human neural stem cells.[62]

August 2006: Mouse Induced pluripotent stem cells: the journal Cell publishes Kazutoshi Takahashi and Shinya Yamanaka.[63]

October 2006: Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[64][65]

January 2007: Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[66] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[67]

June 2007: Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[68] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer [69]

Martin Evans, a co-winner of the Nobel Prize in recognition of his gene targeting work.

October 2007: Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice

using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[70]

November 2007: Human induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of pluripotent stem cells from adult human fibroblasts by defined factors",[71] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced pluripotent stem cell lines derived from human somatic cells":[72] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.

January 2008: Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo[73]

January 2008: Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[74]

February 2008: Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previously developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.[75]

March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences[76]

October 2008: Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial

cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation.[77]

30 October 2008: Embryonic-like stem cells from a single human hair.[78]

1 March 2009: Andras Nagy, Keisuke Kaji, et al. discover a way to produce embryonic-like stem cells from normal adult cells by using a novel "wrapping" procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change.[79][80][81] The use of electroporation is said to allow for the temporary insertion of genes into the cell.[82][83][84][85]

28 May 2009 Kim et al. announced that they had devised a way to manipulate skin cells to create patient specific "induced pluripotent stem cells" (iPS), claiming it to be the 'ultimate stem cell solution'.[86]

11 October 2010 First trial of embryonic stem cells in humans.[87]

25 October 2010: Ishikawa et al. write in the Journal of Experimental Medicine that research shows that transplanted cells that contain their new host's nuclear DNA could still be rejected by the invidual's immune system due to foreign mitochondrial DNA. Tissues made from a person's stem cells could therefore be rejected, because mitochondrial genomes tend to accumulate mutations.[88]

2011: Israeli scientist Inbar Friedrich Ben-Nun led a team which produced the first stem cells from endangered species, a breakthrough that could save animals in danger of extinction.[89]

Stem cell treatmentsFrom Wikipedia, the free encyclopedia

Stem cell treatments are a type of intervention strategy that introduces new cells into damaged tissue in order to treat disease or injury. Many medical researchers believe that stem cell treatments have the potential to change the face of human disease and alleviate suffering.[1]The ability of stem cells to self-

renew and give rise to subsequent generations with variable degrees of differentiation capacities,[2] offers significant potential for generation of tissues that can potentially replace diseased and damaged areas in the body, with minimal risk of rejection and side effects.

See also: Cell therapy

A number of stem cell therapies exist, but most are at experimental stages or costly, with the notable exception of bone marrow transplantation.[citation needed] Medical researchers anticipate that adult and embryonic stem cells will soon be able to treat cancer, Type 1 diabetes mellitus, Parkinson's disease, Huntington's disease, Celiac Disease, cardiac failure, muscle damage and neurological disorders, and many others.[3] Nevertheless, before stem cell therapeutics can be applied in the clinical setting, more research is necessary to understand stem cell behavior upon transplantation as well as the mechanisms of stem cell interaction with the diseased/injured microenvironment.[3]

Contents

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1 Current treatments2 Potential treatmentso 2.1 Brain damageo 2.2 Cancero 2.3 Spinal cord injuryo 2.4 Heart damageo 2.5 Haematopoiesis (blood cell formation)o 2.6 Baldnesso 2.7 Missing teetho 2.8 Deafnesso 2.9 Blindness and vision impairment

o 2.10 Amyotrophic lateral sclerosiso 2.11 Graft vs. host disease and Crohn's diseaseo 2.12 Neural and behavioral birth defectso 2.13 Diabeteso 2.14 Orthopaedicso 2.15 Wound healingo 2.16 Infertility

3 Clinical Trials4 Stem cell use in animalso 4.1 Veterinary applications

4.1.1 Potential contributions to veterinary medicine 4.1.2 Development of regenerative treatment models

4.1.2.1 Significance of stem cell microenvironments 4.1.2.2 Sources of autologous (patient-derived) stem cells

4.1.3 Currently available treatments for horses and dogs suffering from orthopaedic conditions

4.1.4 Developments in Stem Cell Treatments in Veterinary Internal Medicine

5 Embryonic stem cell controversy6 Stem cell treatments around the worldo 6.1 Chinao 6.2 Mexicoo 6.3 South Koreao 6.4 Ukraine

7 See also8 External links9 References

[edit]Current treatments

Further information: Hematopoietic stem cell transplantation

For over 30 years, bone marrow, and more recently, umbilical cord blood stem cells, have been used to treat cancer patients with conditions such as leukaemia and lymphoma.

[4] During chemotherapy, most growing cells are killed by the cytotoxic agents. These agents, however, cannot discriminate between the leukaemia or neoplastic cells, and the hematopoietic stem cells within the bone marrow. It is this side effect of conventional chemotherapy strategies that the stem cell transplant attempts to reverse; a donor's healthy bone marrow reintroduces functional stem cells to replace the cells lost in the host's body during treatment.

[edit]Potential treatments

[edit]Brain damage

Stroke and traumatic brain injury lead to cell death, characterized by a loss of neurons and oligodendrocytes within the brain. Healthy adult brains contain neural stem cells which divide to maintain general stem cell numbers, or become progenitor cells. In healthy adult animals, progenitor cells migrate within the brain and function primarily to maintain neuron populations for olfaction (the sense of smell). Interestingly, in pregnancy and after injury, this system appears to be regulated by growth factors and can increase the rate at which new brain matter is formed.[citation

needed] Although the reparative process appears to initiate following trauma to the brain, substantial recovery is rarely observed in adults, suggesting a lack of robustness.

Stem cells may also be used to treat brain degeneration, such as in Parkinson's and Alzheimer's disease.[5][6]

[edit]Cancer

The development of gene therapy strategies for treatment of intra-cranial tumours offers much promise, and has shown to be successful in the treatment of some dogs;[7] although research in this area is still at an early stage. Using conventional techniques, brain cancer is difficult to treat because it spreads so rapidly. Researchers at the Harvard Medical School transplanted human neural stem cells into the brain of rodents that received intracranial tumours. Within days, the cells migrated into the

cancerous area and produced cytosine deaminase, an enzyme that converts a non-toxic pro-drug into a chemotheraputic agent. As a result, the injected substance was able to reduce the tumor mass by 81 percent. The stem cells neither differentiated nor turned tumorigenic.[8] Some researchers believe that the key to finding a cure for cancer is to inhibit proliferation of cancer stem cells. Accordingly, current cancer treatments are designed to kill cancer cells. However, conventional chemotherapy treatments cannot discriminate between cancerous cells and others. Stem cell therapies may serve as potential treatments for cancer.[9] Research on treating Lymphoma using adult stem cells is underway and has had human trials. Essentially, chemotherapy is used to completely destroy the patients own lymphocytes, and stem cells injected, eventually replacing the immune system of the patient with that of the healthy donor.

[edit]Spinal cord injury

A team of Korean researchers reported on November 25, 2003, that they had transplanted multipotent adult stem cells from umbilical cord blood to a patient suffering from a spinal cord injury and that following the procedure, she could walk on her own, without difficulty. The patient had not been able to stand up for roughly 19 years. For the unprecedented clinical test, the scientists isolated adult stem cells from umbilical cord blood and then injected them into the damaged part of the spinal cord.[10][11]

According to the October 7, 2005 issue of The Week, University of California, Irvine researchers transplanted multipotent human fetal-derived neural stem cells into paralyzed mice, resulting in locomotor improvements four months later. The observed recovery was associated with differentiation of transplanted cells into new neurons and oligodendrocytes- the latter of which forms the myelin sheath around axons of the central nervous system, thus insulating neural impulses and facilitating communication with the brain.[12]

In January 2005, researchers at the University of Wisconsin–Madison differentiated human blastocyst stem cells into neural stem cells, then into pre-mature motor neurons, and finally into spinal motor neurons, the cell type that, in the human body, transmits messages from thebrain to the spinal cord and subsequently mediates motor function in the periphery. The newly generated motor neurons exhibited electrical activity, the signature action of neurons. Lead researcher Su-Chun Zhang described the process as "[teaching] the blastocyst stem cells to change step by step, where each step has different conditions and a strict window of time."

Transformation of blastocyst stem cells into motor neurons had eluded researchers for decades. While Zhang's findings were a significant contribution to the field, the ability of transplanted neural cells to establish communication with neighboring cells remains unclear. Accordingly, studies using chicken embryos as a model organism can be an effective proof-of-concept experiment. If functional, the new cells could be used to treat diseases like Lou Gehrig's disease, muscular dystrophy, and spinal cord injuries.[citation needed]

[edit]Heart damage

Several clinical trials targeting heart disease have shown that adult stem cell therapy is safe, effective, and equally efficient in treating old and recent infarcts.[13] Adult stem cell therapy for treating heart disease was commercially available in at least five continents at the last count (2007).

Possible mechanisms of recovery include:[5]

Generation of heart muscle cells Stimulation of growth of new blood vessels to repopulate

damaged heart tissue Secretion of growth factors Assistance via some other mechanism

It may be possible to have adult bone marrow cells differentiate into heart muscle cells.[5]

[edit]Haematopoiesis (blood cell formation)

The specificity of the human immune cell repertoire is what allows the human body to defend itself from rapidly adapting antigens. However, the immune system is vulnerable to degradation upon the pathogenesis of disease, and because of the critical role that it plays in overall defense, its degradation is often fatal to the organism as a whole. Diseases of hematopoietic cells are called hematopathology. The specificity of the immune cells is what allows recognition of foreign antigens, causing further challenges in the treatment of immune disease. Identical matches between donor and recipient must be made for successful transplantation treatments, but matches are uncommon, even between first-degree relatives. Research using both hematopoietic adult stem cells and embryonic stem cells has provided insight into the possible mechanisms and methods of treatment for many of these ailments.[citation needed]

Fully mature human red blood cells may be generated ex vivo by hematopoietic stem cells (HSCs), which are precursors of red blood cells. In this process, HSCs are grown together with stromal cells, creating an environment that mimics the conditions of bone marrow, the natural site of red blood cell growth. Erythropoietin, a growth factor, is added, coaxing the stem cells to complete terminal differentiation into red blood cells.[14] Further research into this technique should have potential benefits to gene therapy, blood transfusion, and topical medicine.

[edit]Baldness

Hair follicles also contain stem cells, and some researchers predict research on these follicle stem cells may lead to successes in treatingbaldness through an activation of the stem cells progenitor cells. This treatment is expected to work by activating already existing stem cells on the scalp. Later

treatments may be able to simply signal follicle stem cells to give off chemical signals to nearby follicle cells which have shrunk during the aging process, which in turn respond to these signals by regenerating and once again making healthy hair. Most recently, Dr. Aeron Potter of the University of California has claimed that stem cell therapy led to a significant and visible improvement in follicular hair growth[citation needed]. Results from his experiments are under review by the journal Science (journal).

[edit]Missing teeth

In 2004, scientists at King's College London discovered a way to cultivate a complete tooth in mice[15] and were able to grow them stand-alone in the laboratory. Researchers are confident that this technology can be used to grow live teeth in human patients.

In theory, stem cells taken from the patient could be coaxed in the lab into turning into a tooth bud which, when implanted in the gums, will give rise to a new tooth, and would be expected to grow within two months.[16] It will fuse with the jawbone and release chemicals that encourage nerves and blood vessels to connect with it. The process is similar to what happens when humans grow their original adult teeth.

Many challenges remain, however, before stem cells could be a choice for the replacement of missing teeth in the future.[17]

[edit]Deafness

Heller has reported success in re-growing cochlea hair cells with the use of embryonic stem cells.[18]

[edit]Blindness and vision impairment

Since 2003, researchers have successfully transplanted corneal stem cells into damaged eyes to restore vision. "Sheets of retinal cells used by the team are harvested from aborted fetuses, which some people find objectionable." When these sheets are transplanted over the damaged cornea, the stem cells stimulate renewed repair, eventually restore vision.[19] The latest such

development was in June 2005, when researchers at the Queen Victoria Hospital of Sussex, England were able to restore the sight of forty patients using the same technique. The group, led by Dr. Sheraz Daya, was able to successfully use adult stem cells obtained from the patient, a relative, or even a cadaver. Further rounds of trials are ongoing.[20]

In April 2005, doctors in the UK transplanted corneal stem cells from an organ donor to the cornea of Deborah Catlyn, a woman who was blinded in one eye when acid was thrown in her eye at a nightclub. The cornea, which is the transparent window of the eye, is a particularly suitable site for transplants. In fact, the first successful human transplant was a cornea transplant. The absence of blood vessels within the cornea makes this area a relatively easy target for transplantation. The majority of corneal transplants carried out today are due to a degenerative disease called keratoconus.

The University Hospital of New Jersey reports that the success rate for growth of new cells from transplanted stem cells varies from 25 percent to 70 percent.[21]

In 2009, researchers at the University of Pittsburgh Medical center demonstrated that stem cells collected from human corneas can restore transparency without provoking a rejection response in mice with corneal damage.[22]

In January 2012, The Lancet published a paper[23] by Dr. Steven Schwartz, at UCLA's Jules Stein Eye Institute, reporting two women who had gone legally blind from macular degeneration had dramatic improvements in their vision after retinal injections of human embryonic stem cells.

[edit]Amyotrophic lateral sclerosis

Stem cells have resulted in significant locomotor improvements in rats with an Amyotrophic lateral sclerosis-like disease. In a rodent model that closely mimics the human form of ALS, animals were injected with a virus to kill the spinal cord motor nerves which

mediate movement. Animals subsequently received stem cells in the spinal cord. Transplanted cells migrated to the sites of injury, contributed to regeneration of the ablated nerve cells, and restored locomotor function.[24]

[edit]Graft vs. host disease and Crohn's disease

Phase III clinical trials expected to end in second-quarter 2008 were conducted by Osiris Therapeutics using their in-development product Prochymal, derived from adult bone marrow. The target disorders of this therapeutic are graft-versus-host disease and Crohn's disease.[25]

[edit]Neural and behavioral birth defects

This section needs additional citations for verification. Please help improve this article by adding citations to reliable sources. Unsourced material may be challenged and removed. (August 2010)

A team of researchers led by Prof. Joseph Yanai were able to reverse learning deficits in the offspring of pregnant mice who were exposed to heroin and the pesticide organophosphate.[26]

[27] This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost 100 percent, as shown both in behavioral tests and objective brain chemistry tests. Behavioral tests and learning scores of the treated mice showed rapid improvement after treatment, providing results that rivaled non-treated mice. On the molecular level, brain chemistry of the treated animals was also restored to normal. Through the work, which was supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities, the researchers discovered that the stem cells worked even in cases where most of the cells died out in the host brain.

The scientists found that before they die the neural stem cells succeed in inducing the host brain to produce large numbers of

stem cells which repair the damage. These findings, which answered a major question in the stem cell research community, were published in January 2008 in the leading journal, Molecular Psychiatry. Scientists are now developing procedures to administer the neural stem cells in the least invasive way possible - probably via blood vessels, making therapy practical and clinically feasible. Researchers also plan to work on developing methods to take cells from the patient's own body, turn them into stem cells, and then transplant them back into the patient's blood via the blood stream. Aside from decreasing the chances of immunological rejection, the approach will also eliminate the controversial ethical issues involved in the use of stem cells from human embryos.[28]

[edit]Diabetes

Diabetes patients lose the function of insulin-producing beta cells within the pancreas. Human embryonic stem cells may be grown in cell culture and stimulated to form insulin-producing cells that can be transplanted into the patient.

However, clinical success is highly dependent on the development of the following procedures:[5]

Transplanted cells should proliferate Transplanted cells should differentiate in a site-specific manner Transplanted cells should survive in the recipient (prevention

of transplant rejection) Transplanted cells should integrate within the targeted tissue Transplanted cells should integrate into the host circuitry and

restore function[edit]Orthopaedics

Clinical case reports in the treatment of orthopaedic conditions have been reported. To date, the focus in the literature for musculoskeletal care appears to be on mesenchymal stem cells. Centeno et al. have published MRI evidence of increased

cartilage and meniscus volume in individual human subjects.[29]

[30] The results of trials that include a large number of subjects, are yet to be published. However, a published safety study conducted in a group of 227 patients over a 3-4 year period shows adequate safety and minimal complications associated with mesenchymal cell transplantation.[31]

Wakitani has also published a small case series of nine defects in five knees involving surgical transplantation of mesenchymal stem cells with coverage of the treated chondral defects.[32]

[edit]Wound healing

Stem cells can also be used to stimulate the growth of human tissues. In an adult, wounded tissue is most often replaced by scar tissue, which is characterized in the skin by disorganized collagen structure, loss of hair follicles and irregular vascular structure. In the case of wounded fetal tissue, however, wounded tissue is replaced with normal tissue through the activity of stem cells.[33] A possible method for tissue regeneration in adults is to place adult stem cell "seeds" inside a tissue bed "soil" in a wound bed and allow the stem cells to stimulate differentiation in the tissue bed cells. This method elicits a regenerative response more similar to fetal wound-healing than adult scar tissue formation.[33] Researchers are still investigating different aspects of the "soil" tissue that are conducive to regeneration.[33]

[edit]Infertility

Culture of human embryonic stem cells in mitotically inactivated porcine ovarian fibroblasts (POF) causes differentiation into germ cells(precursor cells of oocytes and spermatozoa), as evidenced by gene expression analysis.[34]

Human embryonic stem cells have been stimulated to form Spermatozoon-like cells, yet still slightly damaged or malformed.[35] It could potentially treat azoospermia.

[edit]Clinical Trials

On January 23, 2009, the US Food and Drug Administration gave clearance to Geron Corporation for the initiation of the first clinical trial of an embryonic stem cell-based therapy on humans. The trial aimed evaluate the drug GRNOPC1, embryonic stem cell-derived oligodendrocyteprogenitor cells, on patients with acute spinal cord injury. The trial was dicontinued in November 2011 so that the company could focus on therapies in the "current environment of capital scarcity and uncertain economic conditions”.[36]

As of mid 2010 hundreds of phase III clinical trials involving stem cells have been registered.[37]

[edit]Stem cell use in animals

[edit]Veterinary applications[edit]Potential contributions to veterinary medicine

Research currently conducted on horses, dogs, and cats can benefit the development of stem-cell treatments in veterinary medicine and can target a wide range of injuries and diseases such as myocardial infarction, stroke, tendon and ligament damage, osteoarthritis,osteochondrosis and muscular dystrophy both in large animals, as well as humans.[38][39][40][41] While investigation of cell-based therapeutics generally reflects human medical needs, the high degree of frequency and severity of certain injuries in racehorses has put veterinary medicine at the forefront of this novel regenerative approach.[42] Companion animals can serve as clinically relevant models that closely mimic human disease.[43][44]

[edit]Development of regenerative treatment modelsVeterinary applications of stem cell therapy as a means of tissue regeneration have been largely shaped by research that began with the use of adult-derived mesenchymal stem cells to treat animals with injuries or defects affecting bone,

cartilage, ligaments and/or tendons.[45][46][47] Because mesenchymal stem cells can differentiate into the cells that make up bone, cartilage, tendons, and ligaments (as well as muscle, fat, and possibly other tissues), they have been the main type of stem cells studied in the treatment of diseases affecting these tissues.[46][48] Mesenchymal stem cells are primarily derived from adipose tissue or bone marrow. Since an elevated immune response following cell transplantation may result in rejection of exogenous cells (except in the case of cells derived from a very closely genetically related individual), mesenchymal stem cells are often derived from the patient prior to injection in a process known asautologous transplantation.[49] Surgical repair of bone fractures in dogs and sheep has demonstrated that engraftment of mesenchymal stem cells derived from a genetically different donor within the same species, termed allogeneic transplantation, does not elicit an immunological response in the recipient animal and can mediate regeneration of bone tissue in major bony fractures and defects.[50][51]Stem cells can speed up bone repair in fractures/defects that would normally require extensive grafting, suggesting that mesenchymal stem cell use may provide a useful alternative to conventional grafting techniques.[50][51] Treating tendon and ligament injuries in horses using stem cells, whether derived from adipose tissue or bone-marrow, has support in the veterinary literature.[52][53] While further studies are necessary to fully characterize the use of cell-based therapeutics for treatment of bone fractures, stem cells are thought to mediate repair via five primary mechanisms: 1) providing an antiinflammatory effect, 2) homing to damaged tissues and recruiting other cells, such as endothelial progenitor cells, that are necessary for tissue growth, 3) supporting tissue remodeling over scar formation, 4) inhibitingapoptosis, and

5) differentiating into bone, cartilage, tendon, and ligament tissue.[53][54]

[edit]Significance of stem cell microenvironmentsThe microenvironment into which stem cells are transplanted significantly alters the capacity of engrafted cells for recovery and repair. The microenviroment provides growth factors and other chemical signals that guide appropriate differentiation of transplanted cell populations and direct transplanted cells to sites of trauma or disease. Repair and recovery can then be mediated via three primary mechanisms: 1) formation and/or recruitment of new blood cells to the damaged region; 2) prevention of programed cell death or apoptosis; and 3) suppression of inflammation.[3][49]

[51] To further enrich blood supply to the damaged areas, and consequently promote tissue regeneration, platelet-rich plasma could be used in conjunction with stem cell transplantation.[49][55] The efficacy of some stem cell populations may also be affected by the method of delivery; for instance, to regenerate bone, stem cells are often introduced in a scaffold where they produce the minerals necessary for generation of functional bone.[3][49][51][55]

[edit]Sources of autologous (patient-derived) stem cells

Autologous stem cells intended for regenerative therapy are generally isolated either from the patient's bone marrow or from adipose tissue. The number of stem cells transplanted into damaged tissue may alter efficacy of treatment. Accordingly, stem cells derived from bone marrow aspirates, for instance, are cultured in specialized laboratories for expansion to millions of cells.[51][55] Although adipose-derived tissue also requires processing prior to use, the culturing methodology for adipose-derived stem cells is not as extensive as that for bone marrow-derived cells.[56][57] While it is thought that bone-marrow derived stem cells are preferred

for bone, cartilage, ligament, and tendon repair, others believe that the less challenging collection techniques and the multi-cellular microenvironment already present in adipose-derived stem cell fractions make the latter the preferred source for autologous transplantation.[49]

[edit]Currently available treatments for horses and dogs suffering from orthopaedic conditions

Autologous or allogeneic stem cells are currently used as an adjunctive therapy in the surgical repair of some types of fractures in dogs and horses.[51][58] Autologous stem cell-based treatments for ligament injury, tendon injury, osteoarthritis, osteochondrosis, and sub-chondral bone cysts have been commercially available to practicing veterinarians to treat horses since 2003 in the United States and since 2006 in the United Kingdom. Autologous stem-cell based treatments for tendon injury, ligament injury, and osteoarthritis in dogs have been available to veterinarians in the United States since 2005. Over 3000 privately-owned horses and dogs have been treated with autologous adipose-derived stem cells. The efficacy of these treatments has been shown in double-blind clinical trials for dogs with osteoarthritis of the hip and elbow and horses with tendon damage.[59][60] The efficacy of using stem cells, whether adipose-derived or bone-marrow derived, for treating tendon and ligament injuries in horses has support in the veterinary literature.[52][53]

[edit]Developments in Stem Cell Treatments in Veterinary Internal Medicine

Currently, research is being conducted to develop stem cell treatments for: 1) horses suffering from COPD, neurologic disease, andlaminitis; and 2) dogs and cats suffering from heart disease, liver disease, kidney disease, neurologic disease, and immune-mediated disorder

[edit]Embryonic stem cell controversy

Main article: Stem cell controversy

There is widespread controversy over the use of human embryonic stem cells. This controversy primarily targets the techniques used to derive new embryonic stem cell lines, which often requires the destruction of the blastocyst. Opposition to the use of human embryonic stem cells in research is often based on philosophical, moral or religious objections.[61]

[edit]Stem cell treatments around the world

[edit]China

Stem cell research and treatment is currently being practiced at a clinical level in the People's Republic of China. The Ministry of Health of the People's Republic of China has permitted the use of stem cell therapy for conditions beyond those approved of in Western countries such as the United States, United Kingdom, and Australia. The Western World has scrutinized China for its failed attempts to meet international documentation standards of these trials and procedures, despite the overwhelmingly positive anecdotal results.[62]

Stem cell therapies provided in China utilize a variety of cell types including umbilical cord stem cells and olfactory ensheathing cells. The stem cells are then expanded in centralized blood banks before being used in stem cell treatments. State-funded companies based in theShenzhen Hi-Tech Industrial Zone treat the symptoms of numerous disorders with adult stem cell therapy. Hospitals throughout eastern China provide numerous therapies to patients in

coordination with the stem cell providers. These companies' therapies are currently focused on the treatment of neurodegenerative and cardiovascular disorders. The most radical successes of Chinese adult stem cell therapy have been in treating the brain. These therapies administer stem cells directly to the brain to promote greater motor and brain function in patients with Cerebral Palsy, Alzheimer's, and brain injuries. However, retrospective studies have shown that Chinese use of fetal-derived brain tissue in spinal cord injured human subjects were not as promising as once thought: the phenotype and the fate of the transplanted cells, described as olfactory ensheathing cells, were unknown. As well, perioperative morbidity and lack of functional benefit were identified as the most serious clinical shortcomings.[62] Furthermore, the extent of regulatory policy in the use of stem cell therapies in China is unclear.[63] In the absence of a valid clinical trials protocol, and more regulatory oversight, Western regulatory agencies advise patients and physicians to be cautious when selecting Chinese stem cell therapeutic centers.[62]

[edit]Mexico

Stem cell treatment is currently being practiced at a clinical level in Mexico. An International Health Department Permit (COFEPRIS) is required. This permit allows the use of stem cell types beyond those approved of in Western countries such as the United States or Europe. Stem cell therapies

provided in Mexico utilize patient Adipose, Bone Marrow, or Donor Placenta sources.

[edit]South Korea

In 2005, South Korean scientists claimed to have generated stem cells that were tailored to match the recipient. Each of the 11 new stem cell lines was developed using somatic cell nuclear transfer (SCNT) technology. The resultant cells were thought to match the genetic material of the recipient, thus suggesting minimal to no cell rejection.[64]

This study, however, was eventually discredited as the primary researcher,Dr. Woo Suk Hwang, admitted to using cells obtained from his research staff.[citation needed] In Dec 2005, claims were put forward that his research had been manipulated to wrongfully indicate positive results. Later that month, these claims were confirmed by an academic panel.[65]

[edit]Ukraine

Today, Ukraine is permitted to perform clinical trials of stem cell treatments (Order of the MH of Ukraine № 630 "About carrying out clinical trials of stem cells", 2008) for the treatment of these pathologies: pancreatic necrosis, cirrhosis, hepatitis, burn disease, diabetes, multiple sclerosis, critical lower limb ischemia. The first medical institution granted the right to conduct clinical trials became the "Institute of Cell Therapy"(Kiev).

Stem cell controversyFrom Wikipedia, the free encyclopedia

This article is written in the style of a debate rather than an encyclopedic summary. It may require cleanup to meet Wikipedia's quality standards and make it more accessible to a general audience. Please discuss this issue on the talk page. (January 2011)

The stem cell controversy is the ethical debate primarily concerning the creation, treatment, and destruction of human embryos incident to research involving embryonic stem cells. Not all stem cell research involves the creation, use, or destruction of human embryos. For example, adult stem cells, amniotic stem cells and induced pluripotent stem cells do not involve human embryos at all.

Contents

  [hide]

1 Background2 Viewpointso 2.1 Endorsement

2.1.1 Human potential and humanity 2.1.2 Efficiency 2.1.3 Superiority 2.1.4 Individuality 2.1.5 Viability

o 2.2 Private Funding Concernso 2.3 Moral and Ethical concernso 2.4 Objection

2.4.1 "Better alternatives"3 Ethical Theories4 Stated views of groupso 4.1 Government policy stances

4.1.1 Europe 4.1.2 United States

4.1.2.1 Origins 4.1.2.2 U.S. Congressional response 4.1.2.3 Funding

4.1.3 Asiao 4.2 Church views

4.2.1 Baptists 4.2.2 Catholicism 4.2.3 Methodism 4.2.4 Pentecostalism 4.2.5 The Church of Jesus Christ of Latter-day Saints

o 4.3 Islamic viewo 4.4 Jewish view

5 See also6 References7 External links

[edit]Background

Main article: Stem cell

Since stem cells have the ability to differentiate into any type of cell, they offer something in the development of medical treatments for a wide range of conditions. Treatments that have been proposed include treatment for physical trauma, degenerative conditions, and genetic diseases (in combination with gene therapy). Yet further treatments using stem cells could potentially be developed thanks to their ability to repair extensive tissue damage.[1]

Great levels of success and potential have been shown from research using adult stem cells. In early 2009, the FDA approved the first human clinical trials using embryonic stem cells. Embryonic stem cells are totipotent, and thus can become any other cell type. Adult stem cells, however, are generally limited to differentiating into different cell types of their tissue of origin. However, some evidence suggests that adult stem cell plasticity

may exist, increasing the number of cell types a given adult stem cell can become. In addition, embryonic stem cells are considered more useful for nervous system therapies, because researchers have struggled to identify and isolate neural progenitors from adult tissues. Embryonic stem cells, however, might be rejected by the immune system - a problem which wouldn't occur if the patient received his or her own stem cells.

Some stem cell researchers are working to develop techniques of isolating stem cells that are as potent as embryonic stem cells, but do not require a human embryo.

Some believe that human skin cells can be coaxed to "de-differentiate" and revert to an embryonic state. Researchers at Harvard University, led by Kevin Eggan, have attempted to transfer the nucleus of a somatic cell into an existing embryonic stem cell, thus creating a new stem cell line.[2] Another study published in August 2006 also indicates that differentiated cells can be reprogrammed to an embryonic-like state by introducing four specific factors, resulting in induced pluripotent stem cells.[3]

Researchers at Advanced Cell Technology, led by Robert Lanza, reported the successful derivation of a stem cell line using a process similar to preimplantation genetic diagnosis, in which a single blastomere is extracted from a blastocyst.[4] At the 2007 meeting of the International Society for Stem Cell Research (ISSCR),[5] Lanza announced that his team had succeeded in producing three new stem cell lines without destroying the parent embryos. "These are the first human embryonic cell lines in existence that didn't result from the destruction of an embryo." Lanza is currently in discussions with the National Institutes of Health (NIH) to determine whether the new technique sidesteps U.S. restrictions on federal funding for ES cell research.[6]

Anthony Atala of Wake Forest University says that the fluid surrounding the fetus has been found to contain stem cells that, when utilized correctly, "can be differentiated towards cell types

such as fat, bone, muscle, blood vessel, nerve and liver cells". The extraction of this fluid is not thought to harm the fetus in any way. He hopes "that these cells will provide a valuable resource for tissue repair and for engineered organs as well".[7]

[edit]Viewpoints

The status of the human embryo and human embryonic stem cell research is a controversial issue as, with the present state of technology, the creation of a human embryonic stem cell line requires the destruction of a human embryo. Stem cell debates have motivated and reinvigorated the pro-life movement, whose members are concerned with the rights and status of the embryo as an early-aged human life. They can believe that embryonic stem cell research instrumentalizes and violates the sanctity of life and some also view it as tantamount tomurder.[8] The fundamental assertion of those who oppose embryonic stem cell research is the belief that human life is inviolable, combined with the belief that human life begins when a sperm cell fertilizes an egg cell to form a single cell.

A portion of stem cell researchers use embryos that were created but not used in in vitro fertility treatments to derive new stem cell lines. Most of these embryos are to be destroyed, or stored for long periods of time, long past their viable storage life. In the United States alone, there have been estimates of at least 400,000 such embryos.[9] This has led some opponents of abortion, such as Utah Senator Orrin Hatch, to support human embryonic stem cell research.[10] See Also Embryo donation.

Medical researchers widely submit that stem cell research has the potential to dramatically alter approaches to understanding and treating diseases, and to alleviate suffering. In the future, most medical researchers anticipate being able to use technologies derived from stem cell research to treat a variety of diseases and impairments. Spinal cord injuries and Parkinson's disease are two examples that have been championed by high-profile media

personalities (for instance, Christopher Reeve and Michael J. Fox, who have lived with these conditions, respectively). The anticipated medical benefits of stem cell research add urgency to the debates, which has been appealed to by proponents of embryonic stem cell research.

In August 2000, The U.S. National Institutes of Health's Guidelines stated:

"...research involving human pluripotent stem cells...promises new treatments and possible cures for many debilitating diseases and injuries, including Parkinson's disease, diabetes, heart disease, multiple sclerosis, burns and spinal cord injuries. The NIH believes the potential medical benefits of human pluripotent stem cell technology are compelling and worthy of pursuit in accordance with appropriate ethical standards." [11]

In 2006, researchers at Advanced Cell Technology of Worcester, Massachusetts, succeeded in obtaining stem cells from mouse embryos without destroying the embryos.[12] If this technique and its reliability are improved, it would alleviate some of the ethical concerns related to embryonic stem cell research.

Another technique announced in 2007 may also defuse the longstanding debate and controversy. Research teams in the United States and Japan have developed a simple and cost effective method of reprogramming human skin cells to function much like embryonic stem cells by introducing artificial viruses. While extracting and cloning stem cells is complex and extremely expensive, the newly discovered method of reprogramming cells is much cheaper. However, the technique may disrupt the DNA in the new stem cells, resulting in damaged and cancerous tissue. More research will be required before non-cancerous stem cells can be created.[13][14][15][16]

Update article to include 2009/2010 current stem cell usages in clinical trials.[17][18] The planned treatment trials will focus on the effects of oral lithium on neurological function in people with

chronic spinal cord injury and those that have received umbilical cord blood mononuclear cell transplants to the spinal cord. The interest in these two treatments derives from recent reports indicating that umbilical cord blood stem cells may be beneficial for spinal cord injury and that lithium may promote regeneration and recovery of function after spinal cord injury. Both lithium and umbilical cord blood are widely available therapies that have long been used to treat diseases in humans.

[edit]Endorsement

Embryonic stem cells have the potential to grow indefinitely in a laboratory environment and can differentiate into almost all types of bodily tissue. This makes embryonic stem cells a prospect for cellular therapies to treat a wide range of diseases.[19]

[edit]Human potential and humanity

This argument often goes hand-in-hand with the utilitarian argument, and can be presented in several forms:

Embryos are not equivalent to human life while they are still incapable of surviving outside the womb (i.e. they only have the potential for life).

More than a third of zygotes do not implant after conception.[20]

[21] Thus, far more embryos are lost due to chance than are proposed to be used for embryonic stem cell research or treatments.

Blastocysts are a cluster of human cells that have not differentiated into distinct organ tissue; making cells of the inner cell mass no more "human" than a skin cell.[19]

Some parties contend that embryos are not humans, believing that the life of Homo sapiens only begins when the heartbeat develops, which is during the 5th week of pregnancy,[22] or when the brain begins developing activity, which has been detected at 54 days after conception.[23]

[edit]Efficiency

In vitro fertilization  (IVF) generates large numbers of unused embryos (e.g. 70,000 in Australia alone).[19] Many of these thousands of IVF embryos are slated for destruction. Using them for scientific research uses a resource that would otherwise be wasted.[19]

While the destruction of human embryos is required to establish a stem cell line, no new embryos have to be destroyed to work with existing stem cell lines. It would be wasteful not to continue to make use of these cell lines as a resource.[19]

Abortions are legal in many countries and jurisdictions. The argument then follows that if these embryos are being destroyed anyway, why not use them for stem cell research or treatments?

[edit]Superiority

This is usually presented as a counter-argument to using adult stem cells as an alternative that doesn't involve embryonic destruction.

Embryonic stem cells make up a significant proportion of a developing embryo, while adult stem cells exist as minor populations within a mature individual (e.g. in every 1,000 cells of the bone marrow, only 1 will be a usable stem cell). Thus, embryonic stem cells are likely to be easier to isolate and grow ex vivo than adult stem cells.[19]

Embryonic stem cells divide more rapidly than adult stem cells, potentially making it easier to generate large numbers of cells for therapeutic means. In contrast, adult stem cell might not divide fast enough to offer immediate treatment.[19]

Embryonic stem cells have greater plasticity, potentially allowing them to treat a wider range of diseases.[19]

Adult stem cells from the patient's own body might not be effective in treatment of genetic disorders. Allogeneic embryonic stem cell transplantation (i.e. from a healthy donor) may be more practical in these cases than gene therapy of a patient's own cell.[19]

DNA abnormalities found in adult stem cells that are caused by toxins and sunlight may make them poorly suited for treatment.[19]

Embryonic stem cells have been shown to be effective in treating heart damage in mice.[19]

Embryonic stem cells have the potential to cure chronic and degenerative diseases which current medicine has been unable to effectively treat.

[edit]Individuality

Before the primitive streak is formed when the embryo attaches to the uterus at approximately 14 days after fertilization, a single fertilized egg can split in two to form identical twins, or a pair of embryos that would have resulted in fraternal twins can fuse together and develop into one person (a tetragametic chimera). Since a fertilized egg has the potential to be two individuals or half of one, some believe it can only be considered a potential person, not an actual one. Those who subscribe to this belief then hold that destroying a blastocyst for embryonic stem cells is ethical.[24]

[edit]Viability

Viability  is another standard under which embryos and fetuses have been regarded as human lives. In the United States, the 1973Supreme Court case of Roe v. Wade concluded

that viability determined the permissibility of abortions performed for reasons other than the protection of the woman's health, defining viability as the point at which a fetus is "potentially able to live outside the mother's womb, albeit with artificial aid."[25] The point of viability was 24 to 28 weeks when the case was decided and has since moved to about 22 weeks due to advancement in medical technology. Embryos used in medical research for stem cells are well below development that would enable viability.

[edit]Private Funding Concerns

In the US, only private funded companies are allowed to perform research on human embryonic or fetal stem cells. This fact "precipitates several immediate concerns.". Michele Garfinkel Publicly funded researchers adhere to ethic guidelines, but with private entities guidelines can become blurry. Another concern is since the research is funded privately, who in the public domain can benefit from these new private findings? Just as insurance is only available to those who pay the premium.

[edit]Moral and Ethical concerns

Many questions arises of this concern, Julian Savulescu [26] lists several arguments.

It is liable to abuse. It violates a person's right to individuality, autonomy, self-hood. It allows eugenic selection.

His journal goes into details of the advantages of using stem cell lines mainly for therapeutic reasons with great emphasis on control. The main reason is that if this regeneration practice goes un-check, there will be someone out there that will be "playing Gods."

[edit]Objection[edit]"Better alternatives"

This argument is used by opponents of embryonic destruction as well as researchers specializing in adult stem cell research.

Pro-life supporters often claim that the use of adult stem cells from sources such as umbilical cord blood has consistently produced more promising results than the use of embryonic stem cells.[27] Furthermore, adult stem cell research may be able to make greater advances if less money and resources were channeled into embryonic stem cell research.[28]

Embryonic stem cells have never produced therapies, (to date, adult stem cells have been used in treatment)[29] Moreover, there have been many advances in adult stem cell research, including a recent study where pluripotent adult stem cells were manufactured from differentiated fibroblast by the addition of specific transcription factors.[30] Newly created stem cells were developed into an embryo and were integrated into newborn mouse tissues, analogous to the properties of embryonic stem cells.

This argument remains hotly debated on both sides. Those critical of embryonic stem cell research point to a current lack of practical treatments, while supporters argue that advances will come with more time and that breakthroughs cannot be predicted.

[edit]Ethical Theories

This unreferenced section requires citations to ensureverifiability.

The main ethical theories used by opponents and supporters in this controversy are consequentialism (utilitarianism) and deontological ethics. Consequentialism is the ethical theory that assess the rightness or wrongness of a certain action based on the desirability of the results or the consequences of the action. In

this theory good actions are actions that brings happiness or pleasure to the largest number of people. Unlike consequentialism, deontological ethics primary concern is the action in its self. The word Deon is a Greek word that means duty or obligation. This ethical theory judges the wrongness or rightness of an action based on the conformity of that action with certain norms or principals. Immanuel Kant, a German philosopher expressed his deontological theory using the categorical imperatives. These categorical imperatives are principles that serve to guide the conduct of people. One of Kant’s categorical imperatives says, “always treat persons as ends in themselves and not merely as means to some other end.” If we give to the human embryo the moral status of a person, then under this principle it will be wrong to destroy the human embryo to save the lives of others.

[edit]Stated views of groups

Main article: Stem cell laws

[edit]Government policy stances[edit]Europe

Austria, France, Germany, Ireland, do not allow the production of embryonic stem cell lines,[31] but the creation of embryonic stem cell lines is permitted in Finland, Greece, the Netherlands, Sweden, Italy and the United Kingdom.[31]

[edit]United StatesMain article: Stem cell laws and policy in the United States

[edit]Origins

In 1973, Roe v. Wade legalized abortion in the United States. Five years later, the first successful human in vitro fertilization resulted in the birth of Louise Brown in England. These developments prompted the federal government to create regulations barring the use of federal funds for research that experimented on human embryos.[32] In 1995, the NIH Human Embryo Research Panel

advised the administration of President Bill Clinton to permit federal funding for research on embryos left over from in vitro fertility treatments and also recommended federal funding of research on embryos specifically created for experimentation. In response to the panel's recommendations, the Clinton administration, citing moral and ethical concerns, declined to fund research on embryos created solely for research purposes,[33] but did agree to fund research on left-over embryos created by in vitro fertility treatments. At this point, the Congress intervened and passed theDickey Amendment in 1995 (the final bill, which included the Dickey Amendment, was signed into law by Bill Clinton) which prohibited any federal funding for the Department of Health and Human Services be used for research that resulted in the destruction of an embryo regardless of the source of that embryo.

In 1998, privately funded research led to the breakthrough discovery of Human Embryonic Stem Cells (hESC). This prompted the Clinton Administration to re-examine guidelines for federal funding of embryonic research. In 1999, the president's National Bioethics Advisory Commission recommended that hESC harvested from embryos discarded after in vitro fertility treatments, but not from embryos created expressly for experimentation, be eligible for federal funding. Though embryo destruction had been inevitable in the process of harvesting hESC in the past (this is no longer the case[34][35][36][37]), the Clinton Administration had decided that it would be permissible under the Dickey Amendment to fund hESC research as long as such research did not itself directly cause the destruction of an embryo. Therefore, HHS issued its proposed regulation concerning hESC funding in 2001. Enactment of the new guidelines was delayed by the incoming George W. Bush administration which decided to reconsider the issue.

President Bush announced, on August 9, 2001 that federal funds, for the first time, would be made available for hESC research.

However, the Bush Administration chose to limit taxpayer funding to then-existing hESC cell lines, thereby limiting federal funding to research in which "the life-and-death decision has already been made".[38] The Bush Administration's guidelines differ from the Clinton Administration guidelines which did not distinguish between currently existing and not-yet-existing hESC. Both the Bush and Clinton guidelines agree that the federal government should not fund hESC research that directly destroys embryos.

Neither Congress nor any administration has ever prohibited private funding of embryonic research. Public and private funding of research on adult and cord blood stem cells is unrestricted.

[edit]U.S. Congressional response

In April 2004, 206 out of 500 members of Congress signed a letter urging President Bush to expand federal funding of embryonic stem cell research beyond what Bush had already supported.

In May 2005, the House of Representatives voted 238-194 to loosen the limitations on federally funded embryonic stem-cell research — by allowing government-funded research on surplus frozen embryos from in vitro fertilization clinics to be used for stem cell research with the permission of donors — despite Bush's promise to veto the bill if passed.[39] On July 29, 2005, Senate Majority Leader William H. Frist(R-TN), announced that he too favored loosening restrictions on federal funding of embryonic stem cell research.[40] On July 18, 2006, the Senate passed three different bills concerning stem cell research. The Senate passed the first bill (Stem Cell Research Enhancement Act), 63-37, which would have made it legal for the Federal government to spend Federal money on embryonic stem cell research that uses embryos left over from in vitro fertilization procedures.[41] On July 19, 2006 President Bush vetoed this bill. The second bill makes it illegal to create, grow, and abort fetuses for research purposes. The third bill would encourage research

that would isolate pluripotent, i.e., embryonic-like, stem cells without the destruction of human embryos.

In 2005 and 2007, Congressman Ron Paul introduced the Cures Can Be Found Act,[42] with 10 cosponsors. With an income tax credit, the bill favors research upon non embryonic stem cells obtained from placentas, umbilical cord blood, amniotic fluid, humans after birth, or unborn human offspring who died of natural causes; the bill was referred to committee. Paul argued that hESC research is outside of federal jurisdiction either to ban or to subsidize.[43]

Bush vetoed another bill, the Stem Cell Research Enhancement Act of 2007,[44] which would have amended the Public Health Service Act to provide for human embryonic stem cell research. The bill passed the Senate on April 11 by a vote of 63-34, then passed the House on June 7 by a vote of 247-176. President Bush vetoed the bill on July 19, 2007.[45]

On March 9, 2009, President Obama removed the restriction on federal funding for newer stem cell lines. [46] Two days after Obama removed the restriction, the President then signed the Omnibus Appropriations Act of 2009, which still contained the long-standing Dickey-Wickerprovision which bans federal funding of "research in which a human embryo or embryos are destroyed, discarded, or knowingly subjected to risk of injury or death;"[47] the Congressional provision effectively prevents federal funding being used to create new stem cell lines by many of the known methods.[32] So, while scientists might not be free to create new lines with federal funding, President Obama's policy allows the potential of applying for such funding into research involving the hundreds of existing stem cell lines as well as any further lines created using private funds or state-level funding. The ability to apply for federal funding for stem cell lines created in the private sector is a significant expansion of options over the limits imposed by President Bush, who restricted funding to the 21 viable stem cell lines that were created before he announced his

decision in 2001.[48] The ethical concerns raised during Clinton's time in office continue to restrict hESC research and dozens of stem cell lines have been excluded from funding, now by judgment of an administrative office rather than Presidential or legislative discretion.[49]

[edit]Funding

In 2005 the NIH funded $607 million worth of stem cell research, of which $39 million was specifically used for hESC.[50] Sigrid Fry-Reverehas argued that private organizations, not the federal government, should provide funding for stem-cell research, so that shifts in public opinion and government policy would not bring valuable scientific research to a grinding halt.[51]

In 2005 the State of California took out 3 billion dollars in bond loans to fund embryonic stem cell research in that state.[52]

[edit]Asia

China has one of the most permissive human embryonic stem cell policies in the world. In the absence of a public controversy, human embryo stem cell research is supported by policies that allow the use of human embryos and therapeutic cloning. Iran has banned embryonic stem cell lines. [53]

[edit]Church viewsSee also: Christian views on cloning

[edit]Baptists

The Southern Baptist Convention opposes human embryonic stem cell research on the grounds that "Bible teaches that human beings are made in the image and likeness of God (Gen. 1:27; 9:6) and protectable human life begins at fertilization."[54] However, it supports adult stem cell research as it does "not require the destruction of embryos."[54]

[edit]Catholicism

In regards, to embryonic stem cell research, the Catholic Church affirms that "the killing of innocent human creatures, even if carried out to help others, constitutes an absolutely unacceptable act." The deliberate destruction of a human embryo is incompatible with Roman Catholicdoctrine, according to which, Pontifical Academy for Life has stated that human blastocysts are inherently valuable and should not be voluntarily destroyed as they are "from the moment of the union of the gametes" human subjects with well defined identities. The Church supports research that involves stem cells from adult tissues and the umbilical cord, as it "involves no harm to human beings at any state of development."[55]

[edit]Methodism

In regards, to embryonic stem cell research, the United Methodist Church stands in "opposition to the creation of embryos for the sake of research" as "a human embryo, even at its earliest stages, commands our reverence."[56] However, it supports adult stem cell research, stating that there are "few moral questions" raised by this issue.[56]

[edit]Pentecostalism

The Assemblies of God opposes "the practice of cultivating stem cells from the tissue of aborted fetuses" because it "perpetuates the evil ofabortion and should be prohibited."[57]

[edit]The Church of Jesus Christ of Latter-day Saints

“The First Presidency of The Church of Jesus Christ of Latter-day Saints has not taken a position regarding the use of embryonic stem cells for research purposes. The absence of a position should not be interpreted as support for or opposition to any other statement made by Church members, whether they are for or against embryonic stem cell research.”[58]

[edit]Islamic view

Islam support most forms of stem cell research. Islam’s obligation towards knowledge coupled with its tradition towards not allowing surrogate parenting or embryo adoption, leads many Islamic scholars to believe that the Qur’an can be used to support stem cell research.

To analyze Islam’s stance towards stem cell research, once again the status of the embryo must be determined. In Chapter 23, verse 12-14 the Qur’an teaches:

"We created (khalaqna) man of an extraction of clay, then we sent him, a drop in a safe lodging, then We created of the drop a clot, then we created of the clot a tissue, then We created of the tissue bones, then we covered the bones in flesh; thereafter We produced it as another creature. So blessed be God, the best of creators!"

This passage has been interpreted to indicate that a fetus is perceived as a human life, only later on in the biological development because of the Qur’an’s use of the words “thereafter We produced him as another creature."

The Shari’ah makes a distinction between actual life and potential life, determining that actual life should be afforded more protection than potential life. Thus, under most interpretations of Islamic law, the embryo is not considered a person and the use of it for stem cell research does not violate Islamic law. Also, under this same line of analysis, stem cells from aborted fetuses would also be permitted if the abortion was performed before the fourth month of pregnancy.

Islamic law prohibits surrogate parenting, adoption and the adoption of human embryos due to the importance of determining a child’s true parentage and inheritance rights.12 This would free up any excess embryos for research purposes since under Islamic law, they could not be used by anyone but the couple who created them. The Washington based Islamic Institute stated, ”Under Islamic principle of the ‘purposes and higher causes of the

Shari’ah (Islamic law), we believe it is a societal obligation to perform research on these extra embryos instead of discarding them.” Several Islamic scholars have also pointed out that cloning embryos for therapeutic uses would also be permitted.

Many Islamic scholars also point to the belief that all knowledge emanates from God and that as such, human beings have an obligation to use that knowledge to serve human society.15 Like Judaism, Islam places an obligation on its followers to seek out knowledge, scientific knowledge in particular, since it is a part of human nature as created by God. As stated by Dr. Abdulaziz Sachedina:

”The will of God” in the Koran has often been interpreted as the processes of nature uninterfered with by human action. Hence, in Islam, research on stem cells made possible by biotechnical intervention in the early stages of life is regarded as an act of faith in the ultimate will of God as the Giver of all life, as long as such an intervention is undertaken with the purpose of improving human health.

Thus, Islam’s obligation towards knowledge coupled with its tradition towards not allowing surrogate parenting or embryo adoption, leads many Islamic scholars to believe that the Qur’an can be used to support stem cell research.[59]

[edit]Jewish view

According to Rabbi Levi Yitschak Halperin of the Institute for Science and Jewish Law in Jerusalem, embryonic stem cell research is permitted so long as it has not been implanted in the womb. Not only is it permitted, but research is encouraged, rather than wasting it.

“ As long as it has not been implanted in the womb and it is still a frozen fertilized egg, it does not have the status of an embryo at all and there is no prohibition to destroy it...

”

However in order to remove all doubt [as to the permissibility of destroying it], it is preferable not to destroy the pre-embryo unless it will otherwise not be implanted in the woman who gave the eggs (either because there are many fertilized eggs, or because one of the parties refuses to go on with the procedure - the husband or wife - or for any other reason). Certainly it should not be implanted into another woman.... The best and worthiest solution is to use it for life-saving purposes, such as for the treatment of people that suffered trauma to their nervous system, etc.

—Rabbi Levi Yitschak Halperin, Ma'aseh Choshev vol. 3, 2:6

Similarly, the sole Jewish majority state, Israel, permits research on embryonic stem cells.