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Biotech / Medical : Biotransplant(BTRN) -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (350)	8/15/1999 6:31:00 PM
From: Pseudo Biologist	Read Replies (4) \| Respond to of 1475

Thanks Rick. The abstract pasted below of an earlier paper makes the major point a bit clearer (than the JCI abstract, not than your translation to "human"). The significance of the newer JCI paper is that they have now showed that they can obtain equivalent results with an acceptable "conditioning treatment." The paper below (JEM) used lethal radiation of recipient's marrow, which as the authors state "would not be considered reasonable for use in humans needing organ transplantation." Another novel point of the JCI paper is that this time they do the (heart) transplants and show the potential clinical relevance of the absence of anti-Gal antibodies more dramatically. Which brings another clarification (for myself; this is obvious to Rick, of course): the idea here is to give organ recipients a kind of bone marrow transplant (BMT) from the donor cells before the actual organ. This creates the "mixed chimerism" condition that essentially "teaches" the recipient's cells to "like" donor stuff. When the donor's organ comes in, then it is accepted as "self" without having to live with "poison" like cyclosporin or other, usually toxic, immunosuppressive drugs. So, yes, you add the "inconvenience" of a BMT-like procedure to the actual transplant, but you gain to be free of immunosuppressive crp later in life. If you are talking of doing a pig-to-human transplant, then the Sykes procedure may be the only one having any chance of working versus any kind of immunosuppresive therapy. Rick, the next "obvious" experiment would be to take an actual pig organ and transplant it into an Old World monkey or ape using similar conditioning procedures. How far are they from trying this? Note that attempts as recently as last November (using other techniques) did not look too promising: ncbi.nlm.nih.gov Or maybe this it (but no abstract): ncbi.nlm.nih.gov And here is the older abstract before I forget: J Exp Med 1998 Apr 20;187(8):1335-42 Tolerization of anti-Galalpha1-3Gal natural antibody-forming B cells by induction of mixed chimerism. Yang YG, deGoma E, Ohdan H, Bracy JL, Xu Y, Iacomini J, Thall AD, Sykes M Transplantation Biology Research Center, Surgical Service, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts 02129, USA. Xenotransplantation could overcome the severe shortage of allogeneic organs, a major factor limiting organ transplantation. Unfortunately, transplantation of organs from pigs, the most suitable potential donor species, results in hyperacute rejection in primate recipients, due to the presence of anti-Galalpha1-3Gal (Gal) natural antibodies (NAbs) in their sera. We evaluated the ability to tolerize anti-Gal NAb-producing B cells in alpha1,3-galactosyltransferase knockout (GalT KO) mice using bone marrow transplantation (BMT) from GalT+/+ wild-type (WT) mice. Lasting mixed chimerism was achieved in KO mice by cotransplantation of GalT KO and WT marrow after lethal irradiation. The levels of anti-Gal NAb in sera of mixed chimeras were reduced markedly 2 wk after BMT, and became undetectable at later time points. Immunization with Gal+/+ xenogeneic cells failed to stimulate anti-Gal antibody production in mixed chimeras, whereas the production of non-Gal-specific antixenoantigen antibodies was stimulated. An absence of anti-Gal-producing B cells was demonstrated by enzyme-linked immunospot assays in mixed KO + WT --> KO chimeras. Thus, mixed chimerism efficiently induces anti-Gal-specific B cell tolerance in addition to T cell tolerance, providing a single approach to overcoming both the humoral and the cellular immune barriers to discordant xenotransplantation.*