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 )
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
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.
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
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
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>
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>
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