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  1. 1. Prof Dr Mohamed A. BADR Consultant of Internal Med Diabetology Member Of Mouwasat Internal Med Department Team Cell Transplantion
  2. 2. Tree of embryonic development
  3. 3. Cell transplantation Now: It is not just transplantation of organs & tissues Prevent & Cure diseases
  4. 4. STEM CELLS Capable of both self renewal and differentiation Into at least one or more mature cell types Totipotent Pluripotent
  5. 6. Stem cs on mice ovary              
  6. 9. REVOLUTIONAL DISCOVERIES Stem cell discovered in organs thought not to have Regenerative ability brain and muscles <ul><ul><li>First </li></ul></ul>
  7. 10. STEM CELLS
  8. 11. Second Character of plasticity , transform to different types Neural to hematopoietic Dolly fertilized oocyte by a mammary gld cs nucleus 1977
  9. 14. DOLLY
  10. 16. in November of 1998 when researchers first reported the isolation of human embryonic stem (ES) cells. The discovery, made by Dr. James A. Thomson, a biologist at the University of Wisconsin, Madison, offers great promise for new ways of treating disease. ES cells, which are derived from several-day-old embryos, can theoretically differentiate into virtually any type of human cell, from blood cells to skin cells. Reseachers first reported
  11. 17. Third Human embryonic stem cells Totipotent Unlimited replication (appropriate tissue culture )
  12. 20. Pluripotent stem cells
  13. 21. Transplantation Stem cells Altered cells <ul><li>To correct a genetic defect. </li></ul><ul><li>To provide patient - tailored treatment </li></ul><ul><li>- Modify cell ( re-educate cells) </li></ul><ul><li>- Manipulation of immunological response </li></ul>
  14. 30. Characteristics of Human HSC Cell surface antigen expression CD 34 Dye exclusion Syngeneic, allogeneic, autologous
  15. 31. Indication for HSC transplantation After myeloablation Hematological malignancies Replace diseased tissues of hematologic or immunologic origins
  16. 32. Our absence
  17. 38. Cytokines, chemotherapy, monoclonal antibodies specific to the adhesion molecules Mobilization of HSC
  18. 39. Eliminate all malignant cells Create space for donor cells Suppress the host immune system Have limited severe nonhematopoietic toxicity By TBI alone or in combination with cyclophosphamide conditionning
  19. 40. GVHD Acute Chronic
  20. 42. Islet Transplantation:
  22. 44. University of Minnesota
  23. 47. Pancreas and Islet-cell Transplantation In 1987, the University of Chicago Hospitals established the first pancreas transplant program in Illinois and now performs about 25 pancreas or kidney/pancreas transplants each year. The transplant team performed their first successful islet-cell transplant in 1998.
  24. 49. Pancreatic islet cells Ductal cells hepatocytes Allograft, autograft
  25. 54. Critical variables <ul><li>Cold preservation time < 8 hours </li></ul><ul><li>No of islet cells ~ 6000 IE Kg -1 weight IE = IEQ = indicates islet equivalent which is the No. of cells with diameter 150  m </li></ul><ul><li>Rejection prophylaxis ALG = Anti Lymphocytic Globulin ATG = Anti Thymocyte Globulin </li></ul><ul><li>Site for transplantation portal tract  liver </li></ul>4
  26. 60. Technical factors <ul><li>Cold preservation </li></ul><ul><li>Isolation (uneven) Collagenase (Bacteria derived) Collagenase (Genetic eng.) </li></ul><ul><li>Automated centrifuge (Continuous gradient) cell density </li></ul>
  27. 61. Non specific inflammation Immune-mediated destruction Direct pathway Indirect pathway Recurrence of autoimmunity
  28. 62. Limited supply of human islet tissue Immunosuppressive protocols Inadequate knowledge regarding islet function after transplantation Primary non function and ischemia
  29. 63. Immune reaction
  30. 66. Induction of tolerance Donor specific blood transfusion called linked epitope suppression Implantation into thymus when combined with peripheral T cell depletion
  31. 75. xenotransplantation Use of fetal porcine pancreas
  32. 76. http :// www . expertreviews . org / 00001861h . htm Ethical implications of farming genetically engineered animals for human clinical applications Planned in advance zoonotic infection modify donor in vivo Donor species must have islets with compatible function they can be freshly isolated when needed Xenoreaction, hyperacute rejection Supply of islets is potentially unlimited Disadvantages Advantages
  33. 80. immunoisolation
  34. 85. Gene therapy <ul><li>A therapeutic gene or other nucleic acid e.g. RNA molecule or a synthetic oligonucleotide </li></ul><ul><li>Vector </li></ul><ul><li>A Device - Single gene disorders e.g. haemophylia, muscular dystrophies, hyperlipedimia, some cancers - Complex multigenic disorders e.g. diabetes , Alzheimer </li></ul>
  35. 93. Unlimited areas of exploration example : <ul><li>H.Stem cells </li></ul><ul><li>Islet cells </li></ul><ul><li>Muscle cells </li></ul><ul><li>nerve cells </li></ul><ul><li>Hepatocytes </li></ul><ul><li>Chondrocytes </li></ul><ul><li>Retina </li></ul>
  36. 94. ARGUMENTS AGAINST GENE &STEM CELL THERAPIES 1. Uncertainity & Clinical risks, long term effect 2.Altering human traits not diseases 3.Research on early embryos, unconsenting 4. Expensive, never cost effective, no priority 5. Violate the rights of subsequent genertations ETHICAL CONSIDERATION ?
  37. 95. April 20, 2005 — Editor's Note: For the first time, Japanese investigators have successfully reversed a woman's diabetes by transplanting islets from a living donor's pancreas, according to a research letter published online on April 18 by The Lancet . The donor was a healthy 56-year-old woman, and the recipient was her 27-year-old daughter, who had developed brittle, insulin-dependent diabetes at 15 years of age. Before transplantation, the recipient required daily insulin injections, and she had been admitted to the hospital to control her frequent hypoglycemic episodes. Living-Donor Islet Transplantation: A Newsmaker Interview With Shinichi Matsumoto, MD, PhD Laurie Barclay, MD
  38. 96. TRANSPLANT AVERAGE COST The following chart provides the 1996 national average one year cost per transplant type Heart Liver Kidney Kidney-Pancreas Pancreas Heart-Lung Lung Bone Marrow Cornea Hospital 155800 188900 50600 67300 76200 160400 160400 134500 4000 Immunosuppresants 10300 10300 11300 12500 5100 10300 10300 4100 0 Total 253200 314500 116100 141300 125800 271400 265900 217000 8000