Post on 07-May-2015
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Organ transplantation
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Organ transplantation:
The moving of a whole or partial organ from one body toanother or from a donor site on the patient’s own body.Type of transplants
Autograft
Allograft
Isograft
Xenograft
Split transplant
Domino transplant
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Major organs and Tissue transplant
Thoracic: heart, lung, En bloc heart/lung
Abdomen: liver, kidney, pancreas, small bowel
Others: hands, cornea, skin graft, penis
Tissues, cells, fluids: Islets of Langerhans, BM/ stem cell, blood transfusion, blood vessels,heart valve, bone, skin
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History
1905: First successful human corneal allograft transplant Early 1900’s: The problem of rejection was identified 1951-1959: The immune reaction was identified and
immuno suppressive drugs (cortisone) and azathioprine were used
1954: First successful kidney transplant between identical twin
1963: First successful lung transplant for lung cancer patient
1967: First successful for heart transplant 1970: Cyclosporin was discovered that altered,
transplants from reserched surgery to life-saving treatment
1994: Modern immuno suppression, such as Tacrolimus(Prograf) etc. were introduced in conjunction withcyclosporin
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Stem cell transplantation
Type of stem cell
Haemopoietic stem cell: BM, PB, cord blood
Non-haemopoietic stem cell:
Embryonic stem cell (pleuripotent stem cell) Adult stem cell (somatic stem cell)
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Adult haemopoietic and non-haemopoietec stem cell
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Embryonic stem cell
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Haemopoietic Stem Cell Transplantation
Defined by the source of stem cellBone marrow transplantationPeripheral blood stem cell transplantationCord blood stem cell transplantation
Defined by type of donors Autologous SCT (Autograft) Allogeic SCT (Allograft) Syngeneic SCT (Isograft)
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Route of Stem Cell Administration
Direct tissue injection
Transvascular injection (Local circulation)
Intravenous injection
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Stem cell therapy for MI
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Experience in Human
The hope of stem cell transplantation is to treatment or cure for diseases, such as DM, stroke, spiral injury,
Alzheimer’s disease, Parkinson disease, liver failure, heart disease, MS, ESRD, cancer
Published reports of human stem cell trials Heart disease: Mononuclear BM cell infusion via
coronary A in patients with MI improve function and perfusion at 4-6 month FU
Spinal cord injury: direct injection of stem cell improve motor function in these patients
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Human Genome Project (HGP)
A 13 yrs project complete in 2003
Goal Identify all the approximately 20000-25000
genes in human DNA
Determine the sequences of the 3 billion chemicalbase pairs that make up human DNA
Store the information in databases
Transfer related technologies to the private sector
Address the ethical, legal and social issues thatmay arise from the project
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Gene testing
DNA based test: direct examination of the DNA: DNA probe, DNA sequencing
Biochemical test for gene product
Indication for gene testing1. Carrier screening2. Preimplantation genetic diagnosis3. Prenatal diagnostic testing4. Newborn screening5. Presymptomatic testing for predicting adult onset disorders
such as PCKD6. Presymptomatic testing for estimating the risk of developing
cancers and Alzheimer’s disease 7. Confirmational Dx of a symptomatic individual 8. Forensic/identify testing
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Genetic diseases classification: into 4 types
1. Single-gene: > 6,000 known single gene disorders (1:200 every birth): Thalassemia, Marfan syndrome
2. Multifactorial (complex/polygenic): IHD, HT, Alzheimer’s,DM, Cancer, obesity
3. Chromosomal: Down syndrome (trisomy 21)
4. Mitochondria: rare
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Gene therapy
The process by which DNA Sequence are delivered to cell with the goal of preventing, treating or curing diseases
Gene delivery is now being used to
Deliver genes encoding therapeutic proteins Silence disease-causing genes Deliver viral or bacterial genes as a form of vaccination Replace missing or defective genes Deliver genes that promote growth of new tissue or
stimulate regeneration of damaged tissue Deliver genes that catalyze the destruction of cancer cells
or cause cancer cells to revert back to normal tissue
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Gene Delivery system
Virus vector: Adenovirus, retrovirus
Synthetic vector: lipid
Routes of Administration
Ex-vivo gene therapy
In-vivo gene therapy: local delivery to the target organor IV infusion
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Factors that inhibit gene therapy from becoming an effective treatment for genetic disease
Short-lived nature of gene therapy
Immune response
Problems with viral vectors
Multigenes disorders