Role of Eye Bank Beyond The Cornea - Stem Cells

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The EBAI CME 2013 - 21st and 22nd of September 2013, Golden Valley Resort, Ghodbunder Road, Thane West, Mumbai.

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  • Stem cells are different from other cells of the body in that they have the ability to differentiate into other cell/tissue types. This ability allows them to replace cells that have died. With this ability, they have been used to replace defective cells/tissues in patients who have certain diseases or defects.
  • Adult stem cell research on humans began in the 1960's, first achieving success in the treatment of a patient with severe combined immunodeficiency disorder in 1968. Since the early 1970's, adult stem cells have been successfully used for treatment of immunodeficiencies and leukemias.
  • Schematic representation of corneal epithelial cells. The ocular surface is composed of three epithela, conjunctival, limbal and corneal. Limbal stem cells are located in the palisades of Vogt, the transitional zone between the cornea and the conjunctiva. Limbal stem cells are close to blood vessels. They generate transient amplifying cells that terminally differentiate after a discrete number of cell divisions to corneal epithelial cells and undergo both centripetal migration and vertical migration.
  • Role of Eye Bank Beyond The Cornea - Stem Cells

    1. 1. Role Of Eye Bank Beyond TheRole Of Eye Bank Beyond The Cornea-STEM CELLSCornea-STEM CELLS Dr.Srivalli Kaza 21st September 2013 National EBAI CME, Thane.
    2. 2. ACKNOWLEDGEMENTSACKNOWLEDGEMENTS WAVIKAR EYE INSTITUTE, THANE L.V.PRASAD EYE INSTITUTE, HYDERABAD
    3. 3. Dr.Virender S SangwanDr.Virender S Sangwan Shanti Swaroop Bhatnagar Award 2006 Biotech Products and Process Development and Commercialization Award 2007 ACKNOWLEDGEMENTSACKNOWLEDGEMENTS
    4. 4. What Are Stem Cells?What Are Stem Cells? Stem cells are the raw material from which all of the body’s mature, differentiated cells are made. Stem cells give rise to brain cells, nerve cells, heart cells, pancreatic cells, etc.
    5. 5. Stem Cell – DefinitionStem Cell – Definition A cell that has the ability to continuously divide and differentiate (develop) into various other kind(s) of cells/tissues
    6. 6. Stem Cell – are DynamicStem Cell – are Dynamic Are undifferentiated “master” cell that do not yet have a specific function Can change to one or several different cell types (differentiate) under proper conditions Can undergo unlimited cell division, self-renewal) Stem cell Stem cell Self-renewal Specialized cell (e.g., white blood cell) Differentiate
    7. 7. Major types of Stem CellsMajor types of Stem Cells The two broad types of mammalian stem cells are: (a)embryonic stem cells that are isolated from the inner cell mass of blastocysts, (b)adult stem cells that are found in adult tissues. In a developing embryo, stem cells can differentiate into all of the specialized embryonic tissues. I
    8. 8. Autologous – Stem CellsAutologous – Stem Cells Sources of the patient's own stem cells (autologous) are either the cells from patient's own body or his or her cord blood. For autologous transplants physicians now usually collect stem cells from the peripheral blood rather than the marrow This procedure is easier, unlike a bone marrow harvest, it can take place outside of an operating room and the patient does not have to be under general anaesthesia.
    9. 9. Allogeneic – Stem CellsAllogeneic – Stem Cells  Sources of stem cells from another donor (allogeneic) are primarily relatives (familial-allogeneic) or completely unrelated donors (unrelated- allogeneic). The stem cells in this situation are extracted from either the donor's body or cord blood
    10. 10. Xenogenic - Stem CellsXenogenic - Stem Cells In this stem cells from different species are transplanted, e.g. striatal porcine fetal ventral mesencephalic (FVM) xenotransplants for Parkinson's disease. This has no major ethical concerns and a large amount of tissue is available, however life long immunosupression and risk of rejection are the major limitations
    11. 11. History of Adult Stem Cell ResearchHistory of Adult Stem Cell Research Since the 1970’s, bone marrow transplants have been used for treatment of Immunodeficient and leukemia.
    12. 12. History of Human EmbryonicHistory of Human Embryonic Stem Cell ResearchStem Cell Research In 1998, James Thomson (University of Wisconsin-Madison) isolated cells from the inner cell mass of the blastocyst, and developed the first human embryonic stem cell line in culture. Isolate inner cell mass Culture cells Inner cell mass (forms fetus) Day 5-6 Blastocyst
    13. 13. What Diseases Can beWhat Diseases Can be Cured by Stem Cell TherapiesCured by Stem Cell Therapies Any disease in which there is tissue degeneration can be a potential candidate for stem cell therapies
    14. 14. Major Progress in Several ImportantMajor Progress in Several Important Health problemsHealth problems Alzheimer’s disease Parkinson’s disease Spinal cord injury Heart disease Severe burns Diabetes
    15. 15. Drug TestingDrug Testing Stem cells could allow scientists to test new drugs using human cell line which could speed up new drug development. Only drugs that were safe and had beneficial effects in cell line testing would graduate to whole animal or human testing. It would allow quicker and safer development of new drugs.
    16. 16. Source of Stem Cells for MedicalSource of Stem Cells for Medical therapiestherapies Tens of thousands of frozen embryos are routinely destroyed when couples finish their treatment. These surplus embryos can be used to produce stem cells. Regenerative medical research aims to develop these cells into new, healthy tissue to heal severe illnesses.
    17. 17. Stem Cell Research WorldwideStem Cell Research Worldwide
    18. 18. AdultAdult multipotentmultipotent stem cellsstem cells
    19. 19. Adult Stem CellsAdult Stem Cells
    20. 20. Limbal stem Cell therapyLimbal stem Cell therapy The treatment is known as limbal stem cell therapy, and the patients who received the treatment suffered from chemical burn or genetic disease know as aniridia By replacing the limbal stem cells, the cornea begins to clear up as the cells are replaced with the healthy transparent layer again. CLAuT – 1 month post-op
    21. 21. Limbal stem cellLimbal stem cell CONJUNCTIVA CORNEOSCLERAL LIMBUS CORNEA Peripheral Central TDC PMC Differentiable Compartment Suprabasal cells ®Goblet cells Proliferative Compartment: Basal cells TAC SC TDC PMC
    22. 22. Petri dish Amniotic membrane Limbal Tissue Stem cells Culture techniqueCulture technique Feeder cells
    23. 23. AMG & Limbal Stem CellsAMG & Limbal Stem Cells • More efficient ocular surface reconstruction in severe chemical injuries Ucakhan et al, Cornea 2002
    24. 24. LSCT - IndicationsLSCT - Indications • Chemical Injuries • Stevens Johnson Syndrome • Ocular cicatricial Pemphigoid • Thermal injuries • Severe Shield ulcer • Neurotrophic keratitis Sridhar et al, Am J Ophthal 2000 Shimmura et al, Cornea 2001 Sridhar et al, Ophthalmolgy 2001 Sippel et al, Curr Opin Ophthalmol 2001
    25. 25. Surgical Management-EvolutionSurgical Management-Evolution  Conjunctival transplantation(Thoft,1977)  Keratoepithelioplasty(Thoft,1984)  Limbal Autograft(Kenyon & Tseng,1989)  Keratolimbal Allograft(Tsai & Tseng,1994)  Living related conjunctival Allograft (Kwitko et al 1995)  Human AMG(Tsubota et al,1996)  Limbal Stem cell culture (Pellegrini et al, 1997)  SLET (Sangwan et al, 2012)
    26. 26. Case-I
    27. 27. 16/10/2001 • 25 Years , Male • C/O severe photophobia, decreased vision, watering & burning sensation (OU)- following injury to his face with Sodium hydroxide-1& 1/2 Months ago • Was on Rx with Ciplox e/d, Betagan e/d, Atropine e/d, Moisol e/d, Predforte e/d, Norflox e/o & Tab. Vitamin C
    28. 28. OD
    29. 29. OS
    30. 30. Diagnosis • OU-Chemical Injury(Grade IV) Persistent Epithelial defect
    31. 31. Management • OU-AMG under LA---16/10/2001 • OD-Limbal Transplantation from living related donor(Brother)--- 04/07/2002(9 & 1/2 months) • Advice OD-Prednisolone acetate 1% e/d 1 hourly Ciprofloxacin hydrochloride 0.3% e/d qid Tears Plus e/d qid Tab. Cyclosporin 100 mg 2-2-1 Inj. Methyl Prednisolone 500mg stat
    32. 32. OD OS
    33. 33. 05/09/2002 (1 year) 20/125—>20/80 OD-Penetrating Keratoplasty
    34. 34. CASE-2
    35. 35. 24/09/2001 • OS-Chemical burns(grade II ) Symblepharon Epithelial Defect Retained FB 25/09/2001 • OS-Removal of foreign bodies + AMG under LA
    36. 36. 28/02/2002 (5 months)
    37. 37. OS
    38. 38. PLAN • OS-Symblepharon release + AMG under GA on 28/02/2002
    39. 39. 30/04/2002 (7 months) CF @ 1m OS
    40. 40. 23/05/02(8 months) • OD--Limbal Biopsy under LA 06/06/02(9 months) • OS--Limbal transplantation under LA
    41. 41. 03/07/2002(11 months) OS 20/400-->20/100
    42. 42. 09/10/2002( 1 year) OS 20/40-->20/25P
    43. 43. Research on Stem Cells isResearch on Stem Cells is progressingprogressing inin spite of several restrictions!spite of several restrictions!

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