harish padh [email protected] vice chancellor sardar patel university
DESCRIPTION
Stem Cells: Potential for Therapy. Harish Padh [email protected] Vice Chancellor Sardar Patel University. PROBLEM. Replacement parts needed for transplantation or tissue reconstruction. Tissue Engineering. Solution: STEM CELLS. Replacement parts needed for - PowerPoint PPT PresentationTRANSCRIPT
NIPERD
HARISH [email protected]
VICE CHANCELLORSARDAR PATEL UNIVERSITY
Stem Cells: Potential for Therapy
Replacement parts needed for
transplantation or tissue reconstruction
Tissue Engineering
PROBLEM
Replacement parts needed for
transplantation or tissue reconstruction
Tissue Engineering
Solution: STEM CELLS
Stem CellsStem cells are potentially immortal cells capable of self-renewal and also give rise to differentiated cells
No area of research since gene therapy has evoked so much enthusiasm and hope
Stem cells are body ‘master cells’ Differ from mature cells which are fully committedStem cells are thus reserve supply of replacement cells that multiply when needed Formed at conception & gradually become specialized Our body retains stem cell reserves in various organs to replace diseased tissue As the stem cell reserve gets depleted, we succumb to diseases, disorders and process of aging
Embryonic Stem Cells Longer life span, almost ‘immortal’
High degree of plasticity – Pluripotent
Easier to isolate and cultivate
Limitless supply of cells in culture
More genetic stability Ethical issues Form teratomas Will face immune rejection
Embryonic Stem Cells
Thomson et al Science, 1998
Fischbachand FischbachJ. Clin. Inv. 114:1364
Self-renewal: can divide indefinitely
Can undergo asymmetric division
Retain the capacity to develop into any adult cell type
Properties of Pluripotent Stem Cells
Oct-4 (Pou-Transcription factor)
Stage Specific Embryonic Antigens
SSEA-3SSEA-4
Tumor Recognition Antigens
TRA-1-60TRA-1-81
High Alkaline Phosphatase activity
High Telomerase Activity
Characterization of hES Cells
Karyotyping
Therapeutic Potential
Diabetes 1 Neurodegenerative disorders Myocardial infarction Spinal cord injury Severe liver damage Haematological disorders Severe eye and ear damage
Cell transplantation therapy
HTTP://WWW.YOUTUBE.COM/WATCH?V=CGW19KMCWW4&FEATURE=PLAYER_DETAILPAGE
watch.htm
Homoeostasis
Balance of Cell Supply
EVERYDAY NEED
5 m x 1000 x 40 = 200 billion per day RBC
5000 x 1000 x 40 = 200 million per day WBC
Figure: Measurement of ROS in SKO- and SKOM- infected MEF compared to empty vector. D indicates day hereafter
Stem CellsEmbryonic Stem Cells Adult Stem Cells
Adult Stem Cells
Maintain capacity for self-renewal
Undergo asymmetric division or development
Differentiate to limited subset of cell types
Hematopoietic Fetal liver & spleen, bone marrow, peripheral blood, umbilical cord blood
Liver Portal zone near bile duct
Intestine Crypts
Epidermal Basal layer of skin
Limbal stem cells Pigmented ciliary margin
Breast Epithelium Cap cells and basal layer of mammary gland
Pancreas Islets and ducts
Mesenchymal Bone marrow stroma, adipose tissue
Tooth & EarPlacentaGermline stem cells Testis, Ovary (?)
Adult Stem Cells - Sources
DISEASES THAT CAN BE TREATED WITH CORD BLOOD STEM CELLSCancers
Acute and Chronic Leukemia High-Risk Solid Tumors Hodgkin & Non-Hodgkin Lymphoma Myelodysplastic Syndrome
Blood DisordersBeta Thalassemia Diamond-Blackfan Anemia , Fanconi Anemia, Severe Aplastic Anemia Sickle Cell Disease
Immune DisordersChronic Granulomatous Disease Hystiocytic Disorders Leukocyte Adhesion Deficiency Severe Combined Immunodeficiency Diseases Wiskott-Aldrich Syndrome
Metabolic DisordersKrabbe Disease Hurler Syndrome Metachromatic Leukodystrophy Sanfilippo Syndrome
Cord Blood Registry, www.cordblood.com
Adult Stem Cells Embryonic Stem Cells IPS
Induced pluripotent stem cells ?
iPS cells are a type of pluripotent stem cell from an adult somatic cell, by inducing a "forced" expression of certain genes.
iPS cells believed to be identical to natural pluripotent stem cells, such as embryonic stem cell in many respects, such as
• the expression of certain stem cell genes and proteins, • chromatin methylation patterns, • embryoid body formation, • teratomas formation,• viable chimera formation, • potency and, • differentiability.
A Brief History of iPS Findings
2006
2007
2007
2008
2007
SOX2This intron less gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate.
MYCThe protein encoded by this gene is a multifunctional, nuclear phosphoprotein that plays a role in cell cycle progression, apoptosis and cellular transformation. It functions as a transcription factor that regulates transcription of specific target genes. Mutations, overexpression, rearrangement and translocation of this gene have been associated with a variety of hematopoietic tumors
KLF4 Kruppel-like factor 4 Klf4 functions upstream of Nanog in ES cell self-renewal and in preventing ES cell differentiation. Klf4 interacts directly with Oct4 and Sox2 when expressed at levels sufficient to induce induced pluripotent stem cells
OCT4 (POU class 5 homeobox 1)This gene encodes a transcription factor containing a POU homeodomain. This transcription factor plays a role in embryonic development, especially during early embryogenesis, and it is necessary for embryonic stem cell pluripotency
• New tools for studying development• Development of disease models• Novel cell-based therapies
Patient specific iPS lines could overcome problem of immune rejection• Avoid most ethical considerations
associated with hES cells iPS
Fischbachand Fischbach, J. Clin. Inv. 114:1364
Why are iPS Cells Useful?
FIRST STEM CELL CLINICAL TRIAL APPROVED BY FDA
Food and Drug Administration (FDA) had approved the first-ever clinical trial of stem cell therapy on human subjects, in 2009.
The trial, funded by the biotech company Geron, was to test a procedure to repair spinal cord damage.
The therapy involves the injection of precursor cells into the spine, where the cells will then differentiate into oligodendrocytes, the cells type that sheathes and protects the nerves of the spinal cord.
CLINICAL TRIALS IN WORLD FOR FOLLOWING DISORDERS
Non-Ischemic Congestive Heart FailureChronic Obstructive Pulmonary DiseaseStem Cells Trial in Acute Ischemic StrokeCord Blood Infusion in Children with Cerebral PalsyPeripheral arterial disease (leg blood vessel disease) Severe Intermittent ClaudicationPoor Blood Flow to the HeartType 1 DiabetesType 2 DiabetesFistulas Due to Crohn's Disease Secondary Progressive Multiple Sclerosis Frailty Syndrome
Adult Stem Cell Research Network, www.ascrnetwork.com
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Trounston et al. BMC Medicine 2011, 9: 52
Study Condition Intervention Status
Safety and efficacy of autologous bone marrow stem cells in patients with spinal cord injury
Spinal cord injury
Autologous bone marrow derived stem cells
Recruiting
Mesenchymal stem cells in critical limb ischemia
Critical limb ischemia
Mesenchymal stem cells; Plasmalyte A
Active, not recruiting
Clinical trial to study the efficacy and safety of different doses of bone marrow derived mesenchymal stem cells in patients with critical limb ischemia due to Buergers disease
Critical limb ischemia; Buerger’s disease
Allogenic mesenchymal stem cells; Standard protocol of care
Not yet recruiting
Ex vivo cultured bone marrow derived allogenic MSCs in AMI
Myocardial infarction
Stem cells; Plasmalyte A
Active, not recruiting
Allogenic mesenchymal stem cells in osteoarthritis
Osteoarthritis of knee
Ex-vivo cultured adult allogenic MSCs; Plasmalyte A
Recruiting
www.clinicaltrials.gov
Stem cell clinical trials in India- Present status
Study Condition Intervention Status
Safety and efficacy of autologous bone marrow stem cells for treating osteoarthritis
Osteoarthritis Autologous bone marrow stem cells
Enrolling by invitation
Autologous mesenchymal stem cell transplant for Parkinson’s disease
Parkinson’s disease
Autologous bone marrow derived stem cells
Active, not recruiting
Safety and efficacy of autologous bone marrow stem cells for treating chronic renal failure
Chronic renal failure
Autologpus bone marrow stem cells
Recruiting
Efficacy of autologous bone marrow derived stem cell transplantation in patients with type 2 Diabetes Mellitus
Type 2 Diabetes Mellitus
Stem cell harvest; Angiographic transplantation of stem cells
Unknown
Evaluation of the role of mesenchymal stem cells in the treatment of graft versus host disease
Graft vs Host disease
Mesenchymal stem cell infusion
Unknown
www.clinicaltrials.gov
Study Condition Intervention Status
Efficacy of autologous bone marrow derived stem cell transplantation in patients with Type 2 Diabetes Mellitus-2
Type 2 Diabetes Mellitus
Stem cell transplantation
Unknown
Clinical trial on diabetic foot using peripheral blood derived stem cells for treating critical limb ischemia
Diabetic foot; critical limb ischemia; leg ulcers
Will receive G-CSF and peripheral blood derived mononuclear cells; G-CSF; Standard therapy
Unknown
Safety and efficacy of autologous bone marrow stem cells in treating spinal cord injury
Spinal cord injuries
Laminectomy; Intrathecal
Completed
Pilot study of efficacy of Lactobacillus CD2 Lozenges in preventing high-dose chemotherapy induced oral mucositis in patients undergoing hematopoietic stem cell transplantation
Oral mucositis
Lactobacillus CD2 lozenges
Recruiting
www.clinicaltrials.gov
Study Condition Intervention Status
Study of the monoclonal antibody CT-011 in diffuse large B-Cell lymphoma following autologous stem cell transplantation
Lymphoma, Large cell, diffuse; Lymphoma, Mixed cell, diffuse; Primary Mediastinal Large B-cell lymphoma; Transformed follicular lymphoma; Relapsed
CT-011 Completed
BMAC enhanced coronary artery bypass grafting (CABG)
Congestive heart failure
Harvest SmartPReP2 BMAC system
Recruiting
www.clinicaltrials.gov
Study Condition Intervention Status
Safety and efficacy of autologous bone marrow mononuclear cells in patients with severe critical limb ischemia
Critical limb ischemia
Autologous bone marrow mononuclear cells
Recruiting
Granulocyte colony stimulating factor (G-CSF) in acute liver failure and alcoholic hepatitis
Liver failure, acute
Grnaulocyte colony stimulating factor
Recruiting
G-CSF and erythropoetin in survival of patients with decompensated liver disease
Chronic liver disease
G-CSF+EPO; Placebo
Recruiting
Efficacy of granulocyte colony-stimulating factor and erythropoetin for patients with acute-on-chronic liver failure
Acute on chronic hepatic failure
Granulocyte colony stimulating factor (G-CSF) and Erythropoeitin (EPO); Placebo
Recruiting
www.clinicaltrials.gov
Study Condition Intervention Status
Feasibility study of autologous bone marrow aspirate concentrate for treatment of CLI
Arterial occlusive diseases
SmartPReP2 BMAC system
Active, not recruiting
Safety and efficacy evaluation of two year imatinib treatment in adjuvant gastrointestinal stromal tumor (GIST)
Gastrointestinal stromal tumors
Imatinib mesylate
Active, not recruiting
Study of NTx-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in acute ischemic stroke patients
Stroke Human chorionic gonadotropin (hCG), epoetin alfa (EPO); Saline Placebo
Terminated, Has results
REGENESIS (CA): A study of NTxTM-265: Human Chorionic Gonadotropin (hCG) and Epoetin Alfa (EPO) in acute ischemic stroke patients
Stroke NTxTM-265; rhCG, rEPO; Saline placebo
Terminated
www.clinicaltrials.gov
Study Condition Intervention Status
Chemotherapy in treating patients with acute lymphoblastic leukemia and diffuse non-hodgkin’ s lymphoma
Leukemia; Lymphoma
Asparaginase; cyclophosphamide; cytarabine; daunorubicin hydrochloride; doxorubicin hydrochloride; etoposide; ifosfamide; mercaptopurine; methotrexate; prednisone; vincristine sulfate; conventional surgery; radiation therapy
Unknown
www.clinicaltrials.gov
