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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