interest in stem cells is raising in different field of medicine. The question is : is it successful in Gynecology or it is still too early to say that. The present talk may help to explore this .

1. Stem cells in Gynecology
Fact or fiction
??????

2. Basic criteria of stem cells
1. Self-renews
2. Differentiates
Progenitor cell
Stem cell Stem cell

3. 3/2/2015 Dr. Hariom Yadav
Types
Princeton University

4. Multipotent hematopoietic
Stem cell
(hemocytoblast)
Common myeloid
progenitor
Common Lymphoid
progenitor
Small lymphocyte
B lymphocyte T lymphocyte
Natural killer cell
(Large granular Lymphocyte)
Plasma cell
Monocyte
Macrophage
EosinophilBasophil
Thrombocyte
Megakaryocyte
Erythrocyte Mast cell
Mayeloblast
Neutrophil

5. 3/2/2015 Dr. Hariom Yadav

7. Challenges to Embryonic Stem Cell Research
• Ethical considerations

8. 3/2/2015
Not only ethics
• The use of mouse “feeder” cells to grow ESC could result in problems
due to xenotransplantation (complicating FDA requirements for
clinical use).

9. 3/2/2015
Moreover
• Recently, abnormalities in
chromosome number and structure
were found in three human ESC
lines.

10. 3/2/2015 Dr. Hariom Yadav

11. Other available sources
• Placenta
• Amniotic membranes
• Abortus itself
• ?? Quantity

12. Human MSCs Decline With Age:
1
10,000
1
100,000 1
250,000
1
400,000
1
2,000,000
MSCsperMarrowCells
Newborn Teen 30
Age (Years)
50 80

13. Here comes the importance of A.F stem cells
• amniotic fluid stem cells (AFSCs) provide a novel source :
• their primitive stage,
• low immunogenicity
• easy accessibility.

14. The question is: Fact or Fiction!!!
• urogenital tract
• intrauterine stem cell transplantation
• Infertility

15. Urogenital tract disorders
• Urinary incontinence
• Bladder reconstruction
• Pelvic floor

16. U.I
• stem cell injection for sphincteric muscle regeneration is the subject
of research in a number of centers
• Both animal and human studies have been conducted
• Results are conflicting
• Unresolved question : ??transient or permanent

17. Bladder reconstruction (entero–cystoplasty)
• A tissue–engineered and urothelial–lined bladder provides a
functional barrier against urine exposure
• could help to overcome most of the serious complications associated
with conventional entero–cystoplasty.
• Still under trial
• Results are disappointing

18. Pelvic prolapse
• The idea is to generate new muscle which can perform in an
integrated manner with the existing organs
• Avoid mesh complications (erosions and extrusion)
• Needs to be tested

19. intrauterine stem cell transplantation (IUSCT)
• for monogenic diseases
• to correct a genetic disorder early in the evolution of disease
through the engraftment of normal functional stem cells

20. Quantity needed is much less
• fetal size offers a distinct advantage over the several–fold larger
neonate
• Avoid the need of postnatal bone marrow transplantation

21. Real model
• hfMSC have been collected from the liver of fetus for intrauterine
transplantation targeting osteogenesis imperfect
(Mattar et al, 2012)

22. IUSCT applications
• β–thalassaemia and sickle cell anaemia, muscular dystrophies
• successful treatment has only been achieved in a very few fetuses

23. How it was done?
• Ultrasound or fetoscopy guided fetal liver biopsies
• first trimester
• with very low rate of abortion (8%)
• Others used Amniotic fluid if significant quantity of stem cells can be
derived????

24. The major question is :
• Can this be a complete cure?!!!
• Days will tell.

25. What about infertility: In POF?
• AFSCs were transplanted into the ovaries of mice with POF six weeks
post induction using chemotherapeutic drugs.
• the transplanted AFSCs did not differentiate into germ line cells in
vivo.

26. Stem cells types References
Stem cells and
germ cells
markers
Chemotherapy
Morphologically
of ovary after
stem cells
transplanted
Hormone or cytokines profile
changes
Tracking of stem cells
Bone marrow
transplantation
Lee et al.43 / / /
BMP15, FMR1, FSHR, INHA, AMH,
NOBOX, FOXO3, EIF2B, FIGLA and
GDF9
Reactivate host oogenesis; not
generate oocytes
CD44 +/CD105 +
human amniotic
fluid
mesenchymal
stem cells
Liu et al.73
CD29, CD44,
CD73, CD90,
CD105 and CD166
Intraperitoneal
injection of
cyclophosphamide
/ / /
Adipose-derived
stem cells
Sun et al.63 /
Intraperitoneal
injection of
cyclophosphamide
Follicle number ,
ovulation number
and apoptotic
GCs¯
HGF , VEGF, PGF and TGF-β
Not participate in follicle
regeneration
Umbilical cord
mesenchymal
stem cells
Wang et al.64
CD29, CD44,CD90
and CD105
Intraperitoneal
injection of
cyclophosphamide
Apoptosis of GC¯,
number of
folliclesand oocyte
containing follicles
E2 Not develop into follicles
Human amniotic
fluid cells
Lai et al.72
Intraperitoneal
injection of
cyclophosphamide
and busulphan
Oocytes at all
stages
AMH and FSHR
Differentiated into GCs; not germ
cell

27. Summary of results
• No evidence of differentiation into oocytes
• But risk of developing GC tumour is potential (Botman , 2014)
• So till now, use of stem cells for POF in human is not valid

28. What about male infertility?
• studies have reported differentiation of mouse and human germ cells
from pluripotent stem cells (PSCs) in vitro,
• However, differentiation of human germ cells from SCs in vivo has not
been reported

29. Azoospermia : May 2014

30. Beware
• Testicular teratoma has been reported after SC injection in
azoospermic man

31. human trials?
• Only Two clinical trials are registered in human
• Unfortunately both from the Middle East (Egypt & Jordan)
• Patients accepted such treatments and were eager to take part
because they have no other choice (RBMonline, 2014)

32. Patients asks: Is there any hope??
• Using the patient miserable condition is not ethical
• Taking money from patients in context of clinical research is not
ethical

33. Conclusion
• It is not fiction
• But far from being Fact

34. • Its use should stay within research rather than practice
Keep in Mind