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By:
Ali Khalaf Ali M. Ali
Emad Fathy Emad M. Qasem
Omar 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 cell
e.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 damaged
cells throughout your life
1 stem cell
Classification of stem cells:
• According to their potency:
Progenitor
cells
MultipotentPluripotentTotipotent
• Produce
terminally
differentiated or
specialized 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:
1
Embryonic
tissue
source
Big
ethical
Problem
Classification of stem cells:
• According to their Source:
2
Extra
embryonic
source
Collection
methods
Expansion
media
Classification of stem cells:
• According to their Source:
3
Adult
source
Limited 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.
Implications of stem cells in Gynecology and Obstetrics
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 cells
Treatment of
gynecological tumors
Regenerative 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.
Implications of stem cells in Gynecology and Obstetrics
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 medicine
In the urogenital tract
1. Treatment of Stress Urinary incontinence
(SUI)
Regenerative medicine
In the urogenital tract
Fig. 2.
2. Bladder reconstruction:
• Classic operation : Entero-cystoplasty.
Regenerative medicine
In 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 medicine
In 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 polyglycolic
acid (PGA) scaffolds.
Regenerative medicine
In the urogenital tract
2. Bladder reconstruction:
• Modifications with stem cells:
B. Implantation of scaffolds
Regenerative medicine
In 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 medicine
In the urogenital tract
Composite cystoplasty
Fig.6.
Regenerative medicine
In 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 medicine
In 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 medicine
In 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 medicine
In the urogenital tract
Regenerative medicine
In 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 medicine
In 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 medicine
In 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.
Implications of stem cells in Gynecology and Obstetrics
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.
Implications of stem cells in Gynecology and Obstetrics
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
Implications of stem cells in Gynecology and Obstetrics
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
Implications of stem cells in Gynecology and Obstetrics
• 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_article
s/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
Implications of stem cells in Gynecology and Obstetrics

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Implications of stem cells in Gynecology and Obstetrics

  • 1. By: Ali Khalaf Ali M. Ali Emad Fathy Emad M. Qasem Omar Gaber Amr Ibrahim
  • 2. • 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
  • 3. • Definition • Classification • Sources •Properties • Important points
  • 4. • undifferentiated cells. • retain the capacity for self-renewal. • Can differentiate into specialized cell types. Definition
  • 5. Overview on stem cells: stem cell stem cell SELF-RENEWAL (copying) specialized cell e.g. muscle cell, nerve cell DIFFERENTIATION (specializing)
  • 6. Overview on stem cells: 1 stem cell Self renewal - maintains the stem cell pool 4 specialized cells Differentiation - replaces dead or damaged cells throughout your life 1 stem cell
  • 7. Classification of stem cells: • According to their potency: Progenitor cells MultipotentPluripotentTotipotent • Produce terminally differentiated or specialized 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.
  • 8. Classification of stem cells: • According to their potency: Fig. 1.
  • 9. Classification of stem cells: • According to their Source: 1 Embryonic tissue source Big ethical Problem
  • 10. Classification of stem cells: • According to their Source: 2 Extra embryonic source Collection methods Expansion media
  • 11. Classification of stem cells: • According to their Source: 3 Adult source Limited time for differentiation
  • 12. Classification of stem cells: muscles skin surface of the eye brain breast intestines (gut) bone marrow testicles Source of adult stem cells:
  • 13. 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.
  • 15. 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:
  • 16. Rich resource in gynecology Stem cells Treatment of gynecological tumors Regenerative 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.
  • 18. 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 medicine In the urogenital tract
  • 19. 1. Treatment of Stress Urinary incontinence (SUI) Regenerative medicine In the urogenital tract Fig. 2.
  • 20. 2. Bladder reconstruction: • Classic operation : Entero-cystoplasty. Regenerative medicine In the urogenital tract Fig.4
  • 21. 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 medicine In the urogenital tract
  • 22. 2. Bladder reconstruction: • Modifications with stem cells: B. Implantation of scaffolds with autologus cells in vitro. E.g.: Collagen scaffolds or collagen coated polyglycolic acid (PGA) scaffolds. Regenerative medicine In the urogenital tract
  • 23. 2. Bladder reconstruction: • Modifications with stem cells: B. Implantation of scaffolds Regenerative medicine In the urogenital tract Fig.4
  • 24. 2. Bladder reconstruction: • Modifications with stem cells: C. Combined cystoplasty. Autologous stem cells sheet with de-epithelized pedicled smooth muscle segment. Regenerative medicine In the urogenital tract
  • 26. 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 medicine In the urogenital tract
  • 27. 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 medicine In the urogenital tract
  • 28. 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 medicine In the urogenital tract
  • 29. Regenerative medicine In 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.
  • 30. Regenerative medicine In the urogenital tract • EnSCs as a promising source of stem cells (Autologous stem cells). Fig.7.
  • 31. 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 medicine In the urogenital tract
  • 32. 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.
  • 34. 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
  • 35. 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.
  • 36. 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.
  • 37. Cancer vaccination • Vaccine production Fig. 5.
  • 39. 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).
  • 40. Reproductive biology • several clinical trials regarding EnSCs are underway, Using them in In Vitro fertilization. • Improving Implantation Rates
  • 42. 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).
  • 43. Methods of Intra-uterine fetal therapy • IUSCT • Engraftment of stem cells in embryo to decrease permanent organ damage and improving survival. Genetic manipulation
  • 44. 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
  • 46. • 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
  • 47. • 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
  • 48. • 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_article s/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