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----------------------------------------------------------------------- Cloned Endocrine Cells Transplanted Across Species Function In Host ----------------------------------------------------------------------- WESTPORT, Sep 08 (Reuters) - In the September issue of Nature Medicine, a research article and three commentaries highlight advances in inter-species transplantation of cells, tissues and organs. According to a press release from the journal, publication of these articles was timed to coincide with the Fourth International Congress on Xenotransplantation this week in Nantes, France. In the original research article, Dr. Peter J. Hornsby and colleagues at Baylor College of Medicine in Houston, Texas, report the successful transplantation of bovine adrenocortical cells, derived from a single clone, into adrenalectomized scid mice. Adrenocortical tissue formed by the transplantation replaced the essential functions of the adrenal glands in the mice, according to the researchers. As the mice were immunodeficient there was no immune reaction to the transplanted cells. The researchers point out that the significance of his team's research lies in the fact that "...an endocrine tissue, replacing the host animal's organ, can be derived from a single, normal somatic cell." "The ability to create xenotransplanted clonal endocrine tissue in host animals" they continue, "offers the possibility for...genetic manipulation of the cells before transplantation." Such experiments "...would enable the resolution of multiple questions in endocrine physiology, cell biology and molecular biology." Dr. David H. Sachs of the Massachusetts General Hospital in Boston, Massachusetts, writes in an accompanying News and Views article, "The fact that implantation, organization and function of a relatively normal endocrine tissue occurs in a discordant species when the immune system is compromised emphasizes the important role that the immune system generally plays in preventing successful xenotransplantation." Dr. Sachs acknowledges that, in humans, the immunodeficient state that permitted success in Dr. Hornsby's mice "...would not be clinically acceptable" because of inevitable infectious complications. "For this reason, attempts are underway in our laboratory and elsewhere to modify the immune response of recipients to xenotransplants through the induction of specific tolerance to at least some of the most important T cell stimulatory antigens," he writes. "We have demonstrated that such tolerance is possible in a highly disparate species combination, pig to mouse." In a Commentary article, Dr. Fritz H. Bach and his colleagues at Beth Israel Deaconess Medical Center in Boston discuss genetic manipulation of donor animals to protect xenograft recipients against immune reactions. Rather than systemic administration of immunosuppressive drugs to prevent xenograft rejection, they suggest "...an alternative approach...involving suppression of as many rejection factors as possible by genetically engineering the donor animals and thereby reducing the number of immunosuppressive agents needed and thus the associated toxicity." In the fourth paper, Drs. Ole Isacson and Xandra Breakefield of Massachusetts General Hospital review progress in transplantation of animal cells into human brains. Specifically, they discuss the use of fetal pig neurons to replace dopaminergic neurons in patients with Parkinson's disease and the delivery of a "suicide gene" to brain tumors in humans via a retrovirus vector expressed by transplanted mouse fibroblasts. Clinical trials of both of these techniques are currently underway, according to the authors. Dr. Bach spoke with Reuters Health last week shortly before he left for the Congress in Europe. He summarized the problem that has driven xenotransplantation research: "There's a tremendous shortage of human organs for patients who need them." While efforts are made to convince more people to become donors, "the need is so great that some believe the number of human donors will not suffice." Dr. Bach pointed out that while xenotransplantation is intended to benefit individuals, hazards to the general public must not be overlooked. For instance, he told Reuters Health, "What the real infectious risk is, nobody can say, but it's greater than zero, and that's scary." In the conclusion to their article, he and his colleagues write, "We urge that individuals considering the transplantation of porcine organs and cells to humans take into consideration the potential for infectious risk to the overall population. It seems to us that this factor alone should discourage such transplants until ... we have more prolonged survival or porcine organs transplanted orthotopically to nonhuman primates with documented satisfactory long-term function ... [and] appropriate guidelines for xenotransplantation." Nature Medicine 1997;3:944-948,951-952,964-969,978-982. Copyright 1997 Reuters Limited. <http://www.reutershealth.com/news/docs/199709/19970908sca.html> ----------------------------------------------------------------------- [log in to unmask]