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Spring 1997Volume 4, Number 1 |
Cellular xenografts have been performed extensively in Europe and China,1 but only recently in Sweden and the United States. The most commonly transplanted cells have included insulin-producing tissue from rabbit, porcine, and bovine origin, as well as porcine neurons for treatment of Parkinson's disease. Additional trials have included rat-derived cell lines for treatment of pain, fetal porcine neuronal transplants for treatment of advanced Parkinson's disease, and bone marrow transplantation from non-human primates for treatment of advanced AIDS.2
| Any clinical protocol should be reviewed initially by all members of the xenotransplant team and by the clinical center's biosafety committee, the Institutional Animal Care and Use Committee (IACUC), and the Institutional Review Board (IRB). |
A special symposium was held recently (September 1996) during the Third International Congress of the Cell Transplant Society to address regulatory issues in cell transplantation. At this symposium, Dr. Philip Noguchi from the FDA introduced recently released guidelines from the Department of Health and Human Services on infectious disease issues in xenotransplantation.3 The Public Health Service guidelines represent an attempt to balance the public health risks associated with xenotransplantation with the potential promise of these new biologic replacement strategies. For this purpose, FDA, CDC, and NIH have collaborated to address the concerns that have been raised by recent clinical trials of xenotransplantation (eg, the recent infusion of baboon bone marrow into an AIDS patient).
A few selected issues discussed by the PHS guidelines document are reported here. Multidisciplinary composition of the clinical xenotransplant team is recommended, to include several specialists in addition to transplant physicians and/or surgeons. Specifically, the team should include an infectious disease physician with expertise in zoonoses, transplantation, and microbiology; a veterinarian with specific expertise in the animal husbandry issues and infectious diseases of the animal species serving as the source of transplanted cells; a transplant immunologist; a hospital epidemiologist/infection control specialist; and the director of the clinical microbiology laboratory. The clinical center should also collaborate with an accredited virology and microbiology laboratory with documented expertise in the isolation and identification of unusual and unknown pathogens of both human and veterinary origin.3
Any clinical protocol should be reviewed initially by all members of the xenotransplant team and by the clinical center's biosafety committee, the Institutional Animal Care and Use Committee (IACUC), and the Institutional Review Board (IRB). The committees should have specific expertise in assessment of the potential risk of infection for the contact population, in the evaluation of epidemiological concerns related to conditions of source animal husbandry, and in human and veterinary infectious diseases, including virology, laboratory diagnostics, epidemiology, and risk assessment.
In addition, all live animal cells and tissues are subject to regulation by FDA and the Public Health Service Act and the Federal Food, Drug and Cosmetic Act (42 U.S.C. 262, 264, and 21 U.S.C. 301 et seq). The proposed clinical xenotransplantation protocols should describe methodologies for screening for known infectious agents before transplantation, as well as surveillance after transplantation of the recipients, their contacts, and health care workers.3
Specific points relating to the risk of xenotransplantation should be addressed in the informed consent form, including but not limited to the potential for infection and the potential for transmission of unknown xenogeneic infectious agents, not only to the recipient but also to the recipient's family or close contacts (especially sexual contacts). In addition, the prospective recipient should be informed of any need for isolation procedures during hospitalization, as well as the need to comply with long-term or potentially life-long surveillance, including collection of tissue and/or serum specimens. Furthermore, a xenograft recipient should never donate whole blood, blood components, source plasma, source leukocytes, tissues, breast milk, ova, sperm or any other body parts for use in humans.3
Cells and tissues intended for use in xenotransplantation should be derived only from animals with documented lineages that have been bred and reared in captivity. Animal herds or colonies should be serologically well-characterized. Wild-caught animals should not be used as sources for cells and tissues for any clinical xenograft procedure.3 Additional guidelines address issues related to medical research animal facilities, preclinical screening for unknown infectious agents, herd/colony health maintenance and surveillance, individual source animal screening and qualifications, clinical follow-up and surveillance of the xenotransplant recipient and contacts of recipient, as well as hospital infection control practices and health care records.
A final recommendation underlines how the public health interest would best be served by the establishment of a national registry to enable rapid identification of epidemiologically significant common features among xenograft recipients and provide a database for the assessment of long-term safety.
Camillo Ricordi, MD
Diabetes Research Institute
University of Miami School of Medicine
Miami, Florida
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