By:Ali Khalaf Ali M. Ali

Emad Fathy Emad M. QasemOmar Gaber Amr Ibrahim

• General look on stem cells.

• Gynecology & Obstetrics; a source and a target.

• Stem cells in the regenerative approaches to the urogenital tract.

• Stem cells and Gynecological tumors.

• A way to fight infertility; a reproductive biology point of view.

• Genetic manipulation and fetal genetic therapy.

• Ethical and religious aspects.

Intended learning outcomes

• Definition• Classification• Sources•Properties• Important points

• undifferentiated cells.

• retain the capacity for self-renewal.

• Can differentiate into specialized cell types.

Definition

Overview on stem cells:

stem cell

stem cell

SELF-RENEWAL(copying)

specialized celle.g. muscle cell, nerve cell

DIFFERENTIATION(specializing)

Overview on stem cells:

1 stem cell

Self renewal - maintains the stem cell pool

4 specialized cells

Differentiation - replaces dead or damagedcells throughout your life

1 stem cell

Classification of stem cells:

• According to their potency:

Progenitorcells

MultipotentPluripotentTotipotent

• Produce terminally differentiated orspecialized cells.

• Differentiate into more than 1 type of specialized cells.

• Example:

Hematopoietic stem cells

• From embryonic tissue layers; (ectoderm, endoderm and mesoderm).

• Two types:Embryonic stem (ES)Embryonic Germ (EG)

• Embryonic blastomeres.

• From fertilization up to 8 cells stage

• Give complete organism including extra embryonic tissue.

Classification of stem cells:

• According to their potency:

Fig. 1.

Classification of stem cells:

• According to their Source:

1Embryonic

tissue source

Big ethical

Problem

Classification of stem cells:

• According to their Source:

2Extra

embryonic source

Collection methods

Expansion media

Classification of stem cells:

• According to their Source:

3Adult

sourceLimited time

for differentiation

Classification of stem cells:

muscles

skin

surface of the eye brain

breast

intestines (gut)

bone marrow

testicles

Source of adult stem cells:

Important definitions:

Stem cell engraftment:• This term indicates the homing of the

transfused or transplanted stem cells into a specific target organ.

• Their ability to be functional as evidenced by:

proliferation

expression of differentiation markers.

formation of specialized proteins or structure.

Rich resource in gynecology

• Close contact with the main sources of promising stem cell types;

Embryonic stem cells (ES),

Umbilical cord blood stem cells (UCB)

Fetal stem cells.

As a source:

Rich resource in gynecology

Stem cellsTreatment of

gynecological tumorsRegenerative medicine

approaches

HSC with high dose chemotherapy in

treatment of different types of cancer

Repair and replacement of:

1. Urinary sphincter.2. Pelvic floor.3. Uterus.4. Ovaries.5. Vagina.

1. Treatment of Stress Urinary incontinence (SUI)

• By Autologus stem or Urethral tract progenitor cells.

• Aim : to restore and regenerate muscle content and function of sphincter.

Regenerative medicineIn the urogenital tract

1. Treatment of Stress Urinary incontinence (SUI)

Regenerative medicineIn the urogenital tract

Fig. 2.

2. Bladder reconstruction:

• Classic operation : Entero-cystoplasty.

Regenerative medicineIn the urogenital tract

Fig.4

2. Bladder reconstruction:

• Modifications with stem cells:

A. Using a cellular natural or synthetic biomaterials.

E.g.: small intestinal submucosa, and bladder derived acellular matrix.

Regenerative medicineIn the urogenital tract

2. Bladder reconstruction:

• Modifications with stem cells:

B. Implantation of scaffolds with autologus cells in vitro.

E.g.: Collagen scaffolds or collagen coated polyglycolicacid (PGA) scaffolds.

Regenerative medicineIn the urogenital tract

2. Bladder reconstruction:

• Modifications with stem cells:

B. Implantation of scaffolds

Regenerative medicineIn the urogenital tract

Fig.4

2. Bladder reconstruction:

• Modifications with stem cells:

C. Combined cystoplasty.Autologous stem cells sheet with de-epithelized pedicled

smooth muscle segment.

Regenerative medicineIn the urogenital tract

Composite cystoplastyFig.6.

Regenerative medicineIn the urogenital tract

3. Pelvic floor prolapse (POP) and urinary incontinence (UI):

Ordinary surgical methods:

Repair of the prolapsed bladder

Removal of the uterus (hysterectomy).

Closure of the vagina (vaginal obliteration).

Regenerative medicineIn the urogenital tract

3. Pelvic floor prolapse (POP) and urinary incontinence (UI):

• Biomaterial of synthetic and natural polymers fibers to strength matrix.

• With stem cells used to strengthen and reconstruct muscles of pelvic floor.

Regenerative medicineIn the urogenital tract

3. Uterine reconstruction (endometrial):

• Treatment of women with uterine factor infertility.

• Engraftment of stem cells (from bone marrow source) could produce endometrial tissue regeneration.

Regenerative medicineIn the urogenital tract

Regenerative medicineIn the urogenital tract

• EnSCs as a promising source of stem cells (Autologous stem cells).

• In treatment of critical limb ischaemia, liver cirrhosis , type I diabetes.

Regenerative medicineIn the urogenital tract

• EnSCs as a promising source of stem cells (Autologous stem cells).

Fig.7.

4. Vaginal reconstruction:

• Treatment of vaginal agenesis.

• Ordinary Surgical methods; reconstruction with large intestine or skin.

• Stem cells technique using autologous expanded cells from small vaginal biopsy.

Regenerative medicineIn the urogenital tract

Gynecological theories

Stem cells and endometriosis

• Retrograde menstrual blood stem cells (undifferentiated endometrial stem cells)

• thought to be the etiological factor of both primary disease and its progression to distant sites.

Gynecological tumors

• Embryonal rest theory of cancer:

• It was Postulated that cancer might arise from embryonic like cells.

• Evidence is that cancer cells express embryonic stem cell markers as; OCT-4

Gynecological tumors

Treatment of gynecological tumors

1. Hematopoietic stem cell (HSC)

• Treatment of solid tumors including gynecological.

• High dose chemotherapy.

• Followed by autologous HSC transplantation.

• Adjunctive treatment with different growth factors.

Cancer vaccine-therapy

• Tumor cells can escape the immune control through;

1. Secretion of immuno-suppressive factors.

2. Induction of immune tolerance.

3. Selection of resistant neoplastic clones.

Cancer vaccination

• Vaccine production

Fig. 5.

Reproductive biology

Stem cells and treatment of infertility

• In many ovarian and testicular disorders, they help understanding differentiation and functioning of the gonads.

• Extra-gonadal source of germ cells (from bone marrow).

Reproductive biology

• several clinical trials regarding EnSCs are underway, Using them in In Vitro fertilization.

• Improving Implantation Rates

Genetic manipulation

• New trials in treatment of some genetic diseases as;

1. α-thalassemi.

2. Mucopolusaccharidosis (MPS).

3. Β-thalassemia.

4. Sickle cell anemia.

5. Muscular dystrophies.

6. Osteogenesis Imperfecta (OI).

Methods of Intra-uterine fetal therapy

• IUSCT

• Engraftment of stem cells in embryo to decrease permanent organ damage and improving survival.

Genetic manipulation

Allogenic approaches

• Normal genetic cells transplanted in diseased fetus.

• Mostly Paternal cells.

• Avoidance of breastfeeding.

Autologous approaches

• Cells taken from embryo itself.

• Gene transfer techniques.

• Reintroduction to fetus.

Genetic manipulation

• Stem cells figures: www.eurostemcell.org/files/IntroducingStemCellsFINAL_Jan2012.ppt

• Classification of cells: www.bioline.org.br/pdf?mf06028

• Stem cell therapies in obstetrics and gynecology, Royal college of obstetricians & gynecologists , May 2013, https://www.rcog.org.uk/en/guidelines-research-services/guidelines/sip38/

• Pelvic floor prolapse ordinary surgery methods: http://www.webmd.com/urinary-incontinence-oab/tc/pelvic-organ-prolapse-surgery

• Pelvic floor prolapse (POP) and urinary incontinence (UI) stem cell repair: http://articles.chicagotribune.com/2013-06-03/news/chi-tms-mayo-prolapse_1_pelvic-organ-prolapse-regenerative-medicine-own-cells

• stem cell-based treatments for gynecological solid tumors : http://www.europeanreview.org/wp/wp-content/uploads/160.pdf

• Stem cells and endometriosis: http://cdn.intechopen.com/pdfs-wm/36763.pdf

• Genetic manipulation of stem cells : http://omicsonline.org/genetic-manipulation-of-stem-cells-2161-0932.S6-001.pdf

• Endometrial stem cells in regenerative medicine : http://www.jbioleng.org/content/8/1/20

• Role of Stem Cells in Improving Implantation Rates in ICSI Patients : https://clinicaltrials.gov/ct2/show/NCT01649752

• Fig. 1. : http://en.wikipedia.org/wiki/Stem_cell

• Fig. 2. : http://www.medscape.com/viewarticle/735539

• Fig. 3. : http://www.europeanurology.com/uploads/europeanurology.com/eur_articles/S0302-2838(07)00033-4/assets/gr1.jpg

• Fig. 4. : http://www.mccormick.northwestern.edu/images/news/2013/03/bone-marrow-cells-synthetic-scaffold-used-in-bladder-regeneration-main.jpg

• Fig.5. : http://cvi.asm.org/content/18/1/23/F1.large.jpg .

• Fig.6. : http://openi.nlm.nih.gov/detailedresult.php?img=3098455_gr2&req=4.

• Fig.7. : http://www.jbioleng.org/content/8/1/20/figure/F1