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Prof Dr Mohamed A. BADR Consultant of Internal  Med Diabetology Member Of Mouwasat Internal Med Department Team Cell  Transplantion
Tree of embryonic development
Cell transplantation Now:  It is not just  transplantation of organs & tissues   Prevent & Cure diseases
STEM CELLS Capable of both self  renewal  and  differentiation Into at least one or more mature cell types Totipotent Pluripotent
 
Stem cs on mice ovary              
 
 
REVOLUTIONAL  DISCOVERIES Stem cell discovered in organs thought not to have  Regenerative   ability brain and muscles ,[object Object]
STEM CELLS
Second Character of  plasticity , transform  to different types Neural to hematopoietic  Dolly fertilized oocyte by a mammary gld cs nucleus 1977
 
 
DOLLY
 
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
Third Human embryonic stem cells Totipotent Unlimited replication  (appropriate tissue culture )
 
 
Pluripotent stem cells
Transplantation Stem cells Altered cells ,[object Object],[object Object],[object Object],[object Object]
 
 
 
 
 
 
 
 
Characteristics of Human HSC Cell surface antigen expression CD 34 Dye exclusion Syngeneic, allogeneic, autologous
Indication for HSC transplantation After myeloablation Hematological malignancies Replace diseased tissues of hematologic or immunologic origins
Our absence
 
 
 
 
 
Cytokines, chemotherapy, monoclonal antibodies specific to the adhesion molecules  Mobilization of HSC
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
GVHD Acute Chronic
 
Islet  Transplantation:
EDMONTON CANADA
University of Minnesota
 
 
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.
 
Pancreatic islet cells Ductal cells hepatocytes Allograft,  autograft
 
 
 
 
Critical variables  ,[object Object],[object Object],[object Object],[object Object],4
 
 
 
 
 
Technical factors  ,[object Object],[object Object],[object Object]
Non specific inflammation Immune-mediated destruction Direct pathway Indirect pathway Recurrence of autoimmunity
Limited supply of human islet tissue Immunosuppressive protocols Inadequate knowledge regarding islet function after transplantation Primary non function and ischemia
Immune reaction
 
 
Induction of tolerance Donor specific blood transfusion called linked epitope suppression Implantation into thymus when combined with peripheral T cell depletion
 
 
 
 
 
 
 
 
xenotransplantation Use of fetal porcine pancreas
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
 
 
 
immunoisolation
 
 
 
 
Gene therapy  ,[object Object],[object Object],[object Object]
 
 
 
 
 
 
 
Unlimited areas of exploration example : ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
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   ?
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
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
 

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Transplantation

  • 1. Prof Dr Mohamed A. BADR Consultant of Internal Med Diabetology Member Of Mouwasat Internal Med Department Team Cell Transplantion
  • 2. Tree of embryonic development
  • 3. Cell transplantation Now: It is not just transplantation of organs & tissues Prevent & Cure diseases
  • 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              
  • 7.  
  • 8.  
  • 9.
  • 11. Second Character of plasticity , transform to different types Neural to hematopoietic Dolly fertilized oocyte by a mammary gld cs nucleus 1977
  • 12.  
  • 13.  
  • 14. DOLLY
  • 15.  
  • 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
  • 17. Third Human embryonic stem cells Totipotent Unlimited replication (appropriate tissue culture )
  • 18.  
  • 19.  
  • 21.
  • 22.  
  • 23.  
  • 24.  
  • 25.  
  • 26.  
  • 27.  
  • 28.  
  • 29.  
  • 30. Characteristics of Human HSC Cell surface antigen expression CD 34 Dye exclusion Syngeneic, allogeneic, autologous
  • 31. Indication for HSC transplantation After myeloablation Hematological malignancies Replace diseased tissues of hematologic or immunologic origins
  • 33.  
  • 34.  
  • 35.  
  • 36.  
  • 37.  
  • 38. Cytokines, chemotherapy, monoclonal antibodies specific to the adhesion molecules Mobilization of HSC
  • 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
  • 41.  
  • 45.  
  • 46.  
  • 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.
  • 48.  
  • 49. Pancreatic islet cells Ductal cells hepatocytes Allograft, autograft
  • 50.  
  • 51.  
  • 52.  
  • 53.  
  • 54.
  • 55.  
  • 56.  
  • 57.  
  • 58.  
  • 59.  
  • 60.
  • 61. Non specific inflammation Immune-mediated destruction Direct pathway Indirect pathway Recurrence of autoimmunity
  • 62. Limited supply of human islet tissue Immunosuppressive protocols Inadequate knowledge regarding islet function after transplantation Primary non function and ischemia
  • 64.  
  • 65.  
  • 66. Induction of tolerance Donor specific blood transfusion called linked epitope suppression Implantation into thymus when combined with peripheral T cell depletion
  • 67.  
  • 68.  
  • 69.  
  • 70.  
  • 71.  
  • 72.  
  • 73.  
  • 74.  
  • 75. xenotransplantation Use of fetal porcine pancreas
  • 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
  • 77.  
  • 78.  
  • 79.  
  • 81.  
  • 82.  
  • 83.  
  • 84.  
  • 85.
  • 86.  
  • 87.  
  • 88.  
  • 89.  
  • 90.  
  • 91.  
  • 92.  
  • 93.
  • 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 ?
  • 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
  • 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
  • 97.