Stem cells in GynecologyFact or fiction

??????

Basic criteria of stem cells

1. Self-renews

2. Differentiates

Progenitor cell

Stem cell Stem cell

3/2/2015 Dr. Hariom Yadav

Types

Princeton University

Multipotent hematopoieticStem cell

(hemocytoblast)

Common myeloidprogenitor

Common Lymphoidprogenitor

Small lymphocyte

B lymphocyte T lymphocyte

Natural killer cell(Large granular Lymphocyte)

Plasma cell

Monocyte

Macrophage

EosinophilBasophil

Thrombocyte

Megakaryocyte

Erythrocyte Mast cell Mayeloblast

Neutrophil

3/2/2015 Dr. Hariom Yadav

Challenges to Embryonic Stem Cell Research

• Ethical considerations

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).

3/2/2015

Moreover

• Recently, abnormalities inchromosome number and structurewere found in three human ESClines.

3/2/2015 Dr. Hariom Yadav

Other available sources

• Placenta

• Amniotic membranes

• Abortus itself

• ?? Quantity

Human MSCs Decline With Age:

1

10,000

1

100,000 1

250,0001

400,000

1

2,000,000

MS

Cs

pe

r M

arr

ow

Ce

lls

Newborn Teen 30

Age (Years)

50 80

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.

The question is: Fact or Fiction!!!

• urogenital tract

• intrauterine stem cell transplantation

• Infertility

Urogenital tract disorders

• Urinary incontinence

• Bladder reconstruction

• Pelvic floor

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

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

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

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

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

Real model

• hfMSC have been collected from the liver of fetus for intrauterine transplantation targeting osteogenesis imperfect

(Mattar et al, 2012)

IUSCT applications

• β–thalassaemia and sickle cell anaemia, muscular dystrophies

• successful treatment has only been achieved in a very few fetuses

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????

The major question is :

• Can this be a complete cure?!!!

• Days will tell.

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.

Stem cells types References

Stem cells and

germ cells

markers

Chemotherapy

Morphologically

of ovary after

stem cells

transplanted

Hormone or cytokines profile

changesTracking of stem cells

Bone marrow

transplantationLee 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 cellsSun et al.63 /

Intraperitoneal

injection of

cyclophosphamide

Follicle number ,

ovulation number

and apoptotic

GCs¯

HGF , VEGF, PGF and TGF-βNot participate in follicle

regeneration

Umbilical cord

mesenchymal

stem cells

Wang et al.64CD29, 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 cellsLai et al.72

Intraperitoneal

injection of

cyclophosphamide

and busulphan

Oocytes at all

stages AMH and FSHR

Differentiated into GCs; not germ

cell

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

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

Azoospermia : May 2014

Beware

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

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)

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

Conclusion

• It is not fiction

• But far from being Fact

• Its use should stay within research rather than practice

Keep in Mind