history ,definition,type of stem cells , characters of stem cells , source, stem cell banking , indications of stem cell therapy ,applications in gynaecology

1. STEM CELL THERAPY
-Dr.G.Abirami

2. CONTENTS
• History
• Definition of stem cell
• Types of stem cell
• Characters of stem cell
• Source of stem cell
• Indications of stem cell therapy
• Conclusion

3. HISTORY
• Ancient Greeks - regeneration potential
• 1921 – Alexis carrel – immortal chick embryo cell line
• 1963 – Ernest Mc Culloch and James E Till – landmark publication
• 1981 – Gail Martin and Martin Evans – mouse embryonic stem cells
• 1988 – human embryonic stem cells (University of Wisconsin)
• 2006 – induced pleuripotent stem cells ( genetic reprogramming of
adult cells to assume stem cell like state)

4. STEM CELLS

5. DEFINITION
• Undifferentiated cells
• Capacity for self renewal
• Differentiate into specialized cell types
• Replace damaged or dead cells
.

7. • Stem cells are progenitor cells and they retain
their capacity to divide , differentiate and
replace aging cells

8. TYPE OF STEM CELLS

9. CHARACTERISTICS OF STEM CELLS
• EMBRYONIC STEM CELLS:
 Derived from inner cell mass of the blastocyst
 Rapid engraftment and low immunogenicity
 Indefinite self renewal potential with high telomerase
activity; immortal cells
 Ethical issues , subject to legislation and approval from
religious authorities

10. MESENCHYMAL STEM CELLS
• Derived from bone marrow , adipose tissues,
bone, wharton’s jelly, umbilical cord blood and
peripheral blood
• Differentiates into bone , cartilage , muscle
and adipose tissue
• Limited self renewal with low telomerase
activity.

11. EXTRA EMBRYONIC STEM CELLS:
• Derived from amnion, chorion,placenta and
umbilical cord.
• Multipotent and differentiates into
adipocytes, endothelial cells , hepatocytes,
osteocytes,myocytes and neurons.
• Limites self renewal with low telomerase
activity.

12. iPSCs
• Derived from somatic cells
• Differentiates into cell types of all three germ layers
• Prolonged proliferation
• Indefinite self renewal potential with high telomerase
activity
• Immortal cells

13. SPERMATOGONIAL STEM CELLS
• Derived from testicular tissues
• Differentiates into cell types of all three germ
layers
• Difficult to be maintained in cultures
• Indefinite self renewal potential

14. STEM CELL ENGRAFTMENT
• This term indicates the homing of transfused /
transplanted stem cells into specific target
organ
• Their ability to be functional is evidenced by
- proliferation
- expression of different markers and
- formation of specialized proteins/ structures.

15. SOURCE
• Embryonic stem cells
• Extra embryonic stem cells
• Cord blood stem cells
• Adult stem cells
• Induced pleuripotent stem cells
• Induced multipotent stem cells
• Somatic cell nuclear transfer
• Oocyte somatic cell fusion

16. SAMPLE COLLECTION AND STEM CELL BANKING
• Regulated through instituitional regulatory board
within Good Manufacturing Practice
• UMBILICAL CORD BLOOD: source of HSC and MSC .
Used in haematological diseases.
• FETAL TISSUE : MTP (if any potential application)
• Intrauterine transplantation of hfMSC , collected from
liver can be used for the treatment of
hemoglobinopathies.

17. NON GYNAECOLOGICAL INDICATIONS FOR
STEM CELL THERAPY
• Insulin dependent diabetes mellitus
• Parkinson’s disease
• Heart disease- both ischaemic and
degenerative
• Spinal cord injuries

18. • Haematological disorders – fanconi’s anaemia,
thalassemia
• Malignancy
• Autoimmune disease
• Genetic disorders like mucopolysaccharidosis,
sickle cell anaemia, muscular dystrophies and
osteogenesis imperfecta.

19. APPLICATIONS IN GYNAECOLOGY

20. PELVIC ORGAN PROLAPSE
• Purpose is to generate new muscles which can
perform in an integrated manner with the
existing tissues to provide mechanical support
to the pelvic organs.
• Hybrid biomaterials ( synthetic and naturally
derived polymers ) may be fabricated to
restore pelvic floor function

21. • Biomaterials should have
-good biocompatability
-appropriate biomechanical and biochemical
properties.

22. ENDOMETRIAL REGENERATION
• INDICATION : infertility due to intrauterine
synechiae secondary to tuberculous
endometritis.
• Adult stem cells present a MSC phenotype and
contribute to human endometrial regeneration in
vivo and in vitro
• Engraftment of stem cells derived from bone
marrow (BMDSC) regenerate the endometrial
lining.

23. VAGINAL RECONSTRUCTION
• Indication : vaginal agenesis
• Stem cell therapy using autologous expanded
cells from a small vaginal biopsy.

24. GYNECOLOGICAL TUMOURS
• Embryonic 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 like OCT-4

25. High dose chemotherapy followed by
autologous haematopoietic stem cell
transplantation with various growth factors to
aid regenerative process – New in treatment
of gynaec malignancies.

26. PREMATURE OVARIAN INSUFFICIENCY
• Stem cell therapy is still in reasearch phase.
• ROSE trial: young women with POI may be
able to use their own bone marrow stem cells
to rejuvenate their ovaries and avoid the
effects of premature menopause.

27. STEM CELL AND MALE INFERTILITY
• In Azoospermic male , Spermatogonic Stem
Cells (SSC) obtained by testicular biopsy
combined with in vitro proliferation and
transplantation may solve the problem.
• Limitations with ESC and iPSC including ethical
issues, tumorigenicity, immune rejection, viral
transduction are not with SSCs.

28. STEM CELLS AND ERECTILE DYSFUNCTION
• Penile erection is a neurovascular response
involving an increase in arterial inflow,
relaxation of corpora smooth muscles and
reduction in venous outflow.
• Erectile dysfunction is caused by diabetes,
neuropathies, cavernous nerve injuries , neuro
transmitter imbalance , vascular and
inflammatory disease

29. • Intracavernosal injection of stem cells
improves erectile function mainly due to the
paracrine factors secreted by the injected cells
( cytoprotective , antifibrotic, anti apoptotic)

30. TREATMENT OF STRESS URINARY
INCONTINENCE
• Aim : To restore and regenerate
rhabdomyosphincter muscle content and
function.
• Autologous stem cells or urethral tract progenitor
cells are used.
• Integrate into sphincter complex , differentiates
and lead to sphincter regeneration.

32. BLADDER RECONSTRUCTION
• INDICATION: neurogenic bladder
• Classic procedure : enterocystoplasty
(Where an Ileal patch with functioning mesentry
juxtaposed to create a functional bladder)

33. ENTEROCYSTOPLASTY

34. MODIFICATIONS WITH STEM CELLS
• Acellular natural or synthetic biomaterials –
small intestinal submucosa and bladder
derived acellular matrix.
• Implantation of scaffolds ( cell seeded collagen
coated PGA scaffolds ) preincubated with
autologous stem cells ( wrapped in omentum
within a vascular bed )

35. IMPLANTATION OF SCAFFOLD

36. • Combined / composite cystoplasty utilizing
autologous stem cells with a deepithelized
pedicle smooth muscle segment.

37. INTRAUTERINE STEM CELL
TRANSPLANTATION
• Engraftment of stem cells in embryo to
decrease permanent organ damage and
improving survival.
• Used to correct genetic disorders like
hemoglobinopathies, mucopolysaccharidoses,
inherited immune deficiencies and
osteogenesis imperfecta.

38. • Allogenic transplantation of HSC has high
tolerance, less rejection rate (done before fetal
immune maturity).
• Autologous stem cells from fetal cord blood
sampling or fetal liver biopsy in early pregnancy is
done and the cells are harvested.
• An ex-vivo gene transfer may be done thereafter.
• Fetal MSC can be bioengineered and used for
disease of bone,skin ,liver and heart.

39. CONCLUSION
• Understand the limitations, putative benefits
and the unknown risks.
• Until sufficient evidence regarding efficacy of
therapy, each case should be considered on an
individual basis.

40. REFERENCE
• Das Gupta 10th Edition
• DC Dutta textbook of Obstetrics
• DC Dutta textbook of Gynaecology
• RCOG scientific impact paper number 38
• ESHRE - stem cells in reproductive medicine
• Stem cells as new agents for treatment of
infertility : review article by Vladislav