STEM CELL THERAPY PRESENTED BY DR.GANGA.T JSSMC. MYSORE. Stem cells Rare Primitive cells Definedby their capacity to self renew as well as differentiate into one or more mature cell types. Two broad types seen: A – embryonic stem cells B – adult stem cells Embyronic stem cell Derived from the inner cell mass Pluripotent Can develop into more than 200 different cells Differentiate into cells of the 3 germ cell layers Because of their capacity of unlimited expansion and pluripotency – useful in regenerative medicine Tissue or adult stem cells They produce cells specific to the tissue in which they are found They are relatively unspecialized However they are predetermined to give rise to specific cell types when they differentiate Eg: haematopoietic, bone marrow, neural Properties Self renewal - the ability to go through numerous cycles of cell division while maintaining the undifferentiated state. Potency – the capacity to differentiate into specialized cell types. Totipotent stem cells -cells produced by the first few divisions of the cell . So can form any cell of the embryo as well as the placenta. Pluripotent – these cells differentiate into cells derived from the three germ cell layers. embryonic stem cell, Eg: embryonic germ cell and embryonic carcinoma cells. Multipotent – these cells can produce cells of a closely related family of cells. Eg:haematopoeitic stem cells, neural and mesenchymal stem cells Unipotent – these cells only produce one cell type., but have the property of self renewal which distinguishes them from the non stem cells. Application of stem cells Stem cell research: 1. It provides an ideal model for the study of development of organisms 2. It replaces damaged cells of the body 3. It also aids in drug discovery Regenerative medicine and Therapeutic issues Therapeutic applications of embryonal stem cells –ES cell The potential to form 200 or more cells. Hence used in regenerative medicine in cases like cardiac failure, Parkinsons disease, diabetes. These cells are being coaxed to differentiate into cardiomyocytes, neural stem cells, insulin producing cell and even germ cells. Safety concern Potential to form teratomas after transplantation Hence to produce pure differentiated cells. Risk of transfer of xenopathogens Immunological barriers Rejection- mediated by class 1 MHC and by antigen presenting cells harbouring the class 2 MHC antigen Can be overcome by generating large MHC homozygous ES cell banks, and the production of patient specific ES cell via Somatic Cell Nuclear Transfer. EScells are used as models for developmental biology like early embryonic differentiation and understanding the pathogenesis of specific genetic diseases. Stem cells and diseases The best studied stem cells are the haematopoietic and the male germ cells. Some of the prominent diseases treated include leukemia, anaemia, thallesemia and myelodysplastic syndrome. Allogenic BMT is another well known procedure done. Fetal stem cells Haematopoietic stem cell: charecterised by the presence of CD 34 - Seen in the umbilical cord and fetal liver - Have a higher cloning efficiency and generates more progenitors than adult bone marrow. - They have a huge competitive engraftment advantage relative to the adult bone marrow. - Fetal liver is now used to treat fetuses having X-Linked SCID. Haematopoietic stem cells used in patients whose haematopoietic system has to be replaced They are used in 1.Providing a functional immune system in a person with SCID. 2.Replacing a defective blood system with a functional one who has non malignant genetic disorder like sickle cell anaemia and thallasemia. 3.Restoring the haematopoietic system in cancer patients after treatment. Transplantation can be 1. Autologous 2. Syngeneic 3. Allogenic GVHD is least when there is genetic identity. Other fetal cells are Mesenchymal stem cells-differentiate to bone, fat and cartilage like the adult counterpart. Neural stem cell- they differentiate into neurons, astrocytes and oligodendrocytes. They are the main source of cells for degenerative CNS injury for replacement. Eg: parkinson’s disease Potential application of fetal stem cells In the field of fetal medicine: 1. Non invasive prenatal diagnosis 2. Intrauterine stem cell transplantation 3. Gene therapy Umbilical cord blood stem cells It has both mesenchymal blood cell and haematopoietic stem cells. 1st successful umbilical cord blood transplantation in 1989 in a patient with Fanconi’s anaemia. Haematopoeitic stem cells Derived from bone marrow in adults and umbilical cord blood Option given to the parents regarding stem cell banking during antenatal visits 25% chance that sibling also can have a perfect match Blood is collected from umb cord immediately after delivery about 100- 150cc The number of cells in 1 ml is 40,000 They are stored in blood banks at -196deg celsius in a state of suspended animation and restart their activity on thawing Advantages over bone marrow cells 1. High rate of engraftment 2. More tolerant to tissue matches 3. Less severe GVHD 4. Rarely contaminated with latent virus 5. Easy to collect, not painful 6. Superior proliferative capacity 7. Greater immunological naievity 8. Unlimited supply 9. Lower cost Ailments for which stem cells are being used now Acute leukemias Chronic leukemias Myelodysplastic syndromes Marrow failure Myeloproliferative disorders Lymphoproliferative disorders Phagocyte disorders Inherited disorders like Lesch Nyhan syndrome, beta Thallesemia etc Inherited platelet abnormalities Inherited metabolic disorders like Mucopolysaccharidosis, Hurler’s syndrome, Krabbe disease, Niemann- pick disease etc Histocytic disorders Inherited erythrocyte abnormalities Inherited immune system disorders like ataxia telangectesia, DiGeorge syndrome, SCID etc Plasma cell disorder Malignancies like neuroblastoma, Ewing sarcoma, Renal cell CA etc Trials underway Cardiac disease Diabetes Multiple Sclerosis Muscular Dystrophy Parkinson’s disease Spinal cord injury Stroke Future stem cell application Alzheimer’s Disease Lupus Rheumatoid arthritis Research is going on regarding the use of stem cells for male infertility in mouse However the progeny has severe abnormalities Also recent research suggests that oocyte can be generated from stem cells originating from 1. Bone marrow- haematopoietic stem cells 2. Ovarian surface cells Ethical issues Are we trying to play GOD? Is embryo a person? Will stem cell research encourage embryo destruction and abortions? Guidelines for stem cell research in India Compulsory registration of the existing cell lines to be registered under specific apex bodies in the field Genetic research dealing with human egg or sperm and genetic engineering and then transfer of human blastocysts will not be allowed Research and therapy using fetal/placental stem cell will be allowed Termination of pregnancy cannot be sought for donating fetal tissue for therapeutic or financial benefits All the umbilical cord blood banks should be registered with Drug Controller General of India Research into human cloning is not to be done These guidelines are aimed to encourage development of sound research and therapy, prevent any misuse of human embryos and fetuses and protect patients from fraudulent treatments in the name of stem cell research.
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