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Organ Transplantation

Graft Rejection
    Cellular Mechanisms
    Molecular Mechanisms

Immunsuppressive Agents
    Corticosteroids
    Calcineurine Inhibitors
    Antiproliferative Agents
    Monoclonal Antibodies
    Polyclonal Antibodies
    Side Effects       

Immunotherapy
    Inductive Therapy
    Maintenance Therapy
    Episodic Treatment

Current Areas of Research
    New Drugs
    Drug Efficacy
    Alternative Therapies
        Tolerance
        Tissue Engineering
        Xenotransplantation

Glossary of Terms
References

TISSUE ENGINEERING

Tissue Engineering has several applications as a substitutive therapy for organ transplantation. The first generation of tissue engineering is the creation of immunoisolated devices that combine living cells and biomaterials. This technique uses hydrogel membranes as a barrier of the foreign living cells from the lymphocytes of the immunocompetent host. This effectively eliminates the need for immunosuppressive therapy. Potential products are bioartificial kidneys, livers, and pancreases.

This approach has very realistic possibilities for medical devices and treatment. In fact, Type I Diabetes has been cured in mice. Encapsulated insulin secreting beta cells were placed in diabetic mice to modulate blood sugar. The cells were able to effectively mimic native beta cell activity in the mice while avoiding immune detection and rejection. However, all to date attempts to apply this successful model to larger animals have failed due to scaling issues.

The future of tissue engineering products is with the advent of stem cells and therapeutic cloning. The technology of harvesting embryonic pluripotent stem cells from the inner cell mass of blastocysts introduces the potential to produce any type of cell using the appropriate cues for differentiation. This technique would enable biologists to grow any functional tissue or organ. The need for immunosuppression for this technique could be circumvented through therapeutic cloning. This is a process where autologous stem cells are used to tissue engineer organs for transplantation. The organs would be inherently "self" organs, with self-antigens. Correspondingly, the immune system would have no incentive to attack the graft. Drawbacks to this therapy include manufacturing problems: because each organ must be created specifically for each individual, there would be a time space between identification of the need for a transplant, and production of a fully functional autograft.

Other problems include the ethical issues surrounding stem-cell research. Despite the substantial contribution embryonic stem cells could bestow to organ transplantation medicine, there are many points of controversy. A point of debate surrounds the idea of when an embryo achieves the status of an individual. Most biologists believe the individualization of the embryo takes place at the formation of the "primitive streak." This is the point where the embryo develops the very beginnings of a nervous system, and both twinning and recombination are no longer possible. Other individuals, led mainly by religious groups, argue that individuality and "humanness" are obtained at conception, and that a soul exists as soon as the sperm penetrates the egg. Controversy on this issue is not surprising, considering that many of the issues parallel the politically charged issue of abortion.

Currently, human embryonic stem cells are heavily regulated by the government and viewed by many as ethical repulsive. An attempt to circumvent using embryonic stem cells includes using ethically uncomplicated adult stem cells that have the ability to transdifferentiate across cell type lineage (proven by Verfaille in 2000). Pre-clinical studies on adult stem cell based therapies have been inconsistent, with many resulting in contradicting outcomes. Results of several allegedly successful studies cannot be repeated reliably. As an example, Orlic's use of marrow-derived adult stem cells to regenerate a significant amount (60%) of necrotic tissue in an infarcted murine cardiac zone was seriously questioned when two other reputable groups were unable to duplicate results.

Despite problems, it is important to note that tissue engineering is in fact a developing therapy. Tissue engineering holds much promise, and with time, money, and research, the early problems currently encountered will almost certainly be worked out. If successful, tissue engineering will dynamically change the field of organ transplantation.

Drug Therapy Research
New Drugs Drug Efficacy
Alternate Therapies
Tolerance Tissue Engineering Xenotransplantation