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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

XENOTRANSPLANTATION

As stated, a major barrier to the success of organ transplantation is mismatch between supply and demand for donor organs, with demand far outstripping supply. Xenotransplantation is a promising therapy that can solve the sourcing problem of organ transplants. With the recent development of transgenic and knock out bioengineered animal clones, this technology has become a realistic goal that has the potential to completely revolutionize transplantation therapy and perhaps eliminate the need for immunosuppressant treatment.

Xenotransplantation is the replacement of an individual's defective organ with an organ harvested from another species. Possible animals considered as a source of organs for human use include primates (because of their genetic similarities to humans) and pigs (because of their large availability). Due to logistic problems in raising primates (including time needed to multiply and reach maturity), focus on pig sourcing currently dominates. In fact, a transgenic, knock out pig is an ideal potential source of xenotransplants. The pig is a model candidate due to its human-comparable organ size, large litters, and rapid gestation. Pig Pharms (the term for a breeding facility for such pigs) could potentially breed and raise sterile pigs in a controlled environment that is both free of specific pathogens and a known bacterial load. Thus, Pig Pharms have the potential to resolve organ-sourcing problems.

Pig Pharms - these genetically engineered pigs are possible sources of cardiac xenografts.

In order to become a successful solution for organ transplantation, xenotransplantation needs to overcome multiple biological barriers. The main problem is obvious but formidable: the species difference correlates to a higher degree of antigen disparity. In other words, there is significantly more for the immune system to recognize and reject. One such problem antigen is carbohydrate expressed on the cell surface of many animals: alpha-gal. This antigen is thought to be the main culprit behind the hyperacute and acute vascular humoral rejections observed in xenotransplantation. If xenotransplantation is to be clinically acceptable, reactions to such xenoantigens must be stifled.

Porcine Endogenous Retroviruses (PERVs) have been detected in pig cells. This is one of the main reasons why people are sceptical of xenotransplantation.

Current areas of research concentrate on this problem. At this time, scientists have successfully bypassed hyperacute rejection by manipulating the donor xenograft endothelial system expression of complement inhibitory proteins and knocking out genes for the carbohydrate alpha-gal. However, the struggle to fully eliminate acute vascular rejection still remains. However, as both therapeutic cloning and stem cell technology improve, it can be predicted that xenotransplantation will become more realistically feasible.

Other barriers to xenotransplantation include the possibility of diseases "jumping" the species barrier and infecting humans. One such cause of reservation is a group of infectious agents known as Porcine Endogonous Retroviruses (PERV). This possibility has done much to decrease enthusiasm in the investigation of xenotransplantation as an alternative to allogeneic organ transplantation.

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