{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T07:18:49Z","timestamp":1789370329595,"version":"build-2803163510"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2002,2,6]],"date-time":"2002-02-06T00:00:00Z","timestamp":1012953600000},"content-version":"vor","delay-in-days":36,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Xenotransplantation"],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:p>The aim of the present study was to assess the survival of adult porcine islets transplanted into baboons receiving either (1) conventional triple drug immunosuppressive therapy or (2) a non\u2010myeloablative regimen and an anti\u2010CD154 monoclonal antibody (mAb) aimed at tolerance\u2010induction.<\/jats:p><jats:p>Group 1 baboons (n=3) were pancreatectomized prior to intraportal injection of 10\u2003000 porcine islet equivalents (IE)\/kg and immunosuppressed with anti\u2010thymocyte globulin (ATG), cyclosporine and azathioprine. In Group 2 (n=2), non\u2010pancreatectomized baboons underwent induction therapy with whole body and thymic irradiation, and ATG. Extracorporeal immunoadsorption (EIA) of anti\u2010Gal\u03b11,3Gal (Gal) antibody was carried out. Maintenance therapy was with cobra venom factor, cyclosporine, mycophenolate mofetil, methylprednisolone and anti\u2010CD154 mAb. Porcine islets were injected intraportally (14\u2003000 and 32\u2003000 IE\/kg, respectively) and high\u2010dose pig mobilized peripheral blood progenitor cells (3\u2003\u00d7\u200310<jats:sup>10<\/jats:sup> cells\/kg) were infused into a systemic vein. Porcine islets were also implanted in the sternomastoid muscle to facilitate subsequent biopsies. In both groups, porcine C\u2010peptide was measured, and histological examination of liver or sternomastoid muscle biopsies was performed at regular intervals.<\/jats:p><jats:p>In Group 1, total pancreatectomy reduced human C\u2010peptide to &lt;\u200a0.1\u2003ng\/ml and induced insulin\u2010requiring diabetes. The transplantation of porcine islets was followed by normalization of glycemia for 15\u201324\u2003h. Porcine C\u2010peptide was detected only transiently immediately after porcine islet injection (maximum 0.12\u2003ng\/ml). Histological examination of liver biopsies taken between days 2 and 19 did not reveal viable islets, but necrotic cell structures with mononuclear cell infiltrates were identified in portal venules. In Group 2, injection of porcine islets into non\u2010pancreatectomized recipients induced a transient hypoglycemia (2\u20134\u2003h) requiring concentrated intravenous dextrose administration. Porcine C\u2010peptide was detectable for 5 and 3\u2003days (maximum 2.8 and 1.0\u2003ng\/ml), respectively. Baboon #4 died on day 12 from small bowel intussusception. Liver and sternomastoid muscle biopsies showed well\u2010preserved porcine islets, staining positive for insulin and glucacon, without signs of rejection. In baboon #5, viable islets were detected in the sternomastoid muscle biopsy on day 14, but not on day 28 or thereafter. A progressive mononuclear cell and macrophage infiltration was seen in the biopsies. In conclusion, conventional immunosuppression allowed survival of porcine islets in baboons for\u2003&lt;\u200a24\u2003h. The non\u2010myeloablative regimen prolonged survival of porcine islets for\u2003&gt;\u200314\u2003days. However, despite depletion of T cells, anti\u2010Gal antibody and complement, and CD154\u2010blockade, porcine islets were rejected by day 28. These results suggest that powerful innate immune responses are involved in rejection of discordant xenogeneic islets.<\/jats:p>","DOI":"10.1034\/j.1399-3089.2002.1o044.x","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T07:54:33Z","timestamp":1027670073000},"page":"3-13","source":"Crossref","is-referenced-by-count":87,"title":["Adult porcine islet transplantation in baboons treated with conventional immunosuppression or a non\u2010myeloablative regimen and CD154 blockade"],"prefix":"10.1111","volume":"9","author":[{"given":"L.","family":"B\u00fchler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"O'Neil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Kitamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Koulmanda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Baldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Rahier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.P.J.","family":"Alwayn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.Z.","family":"Appel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Awwad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.H.","family":"Sachs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Weir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.P.","family":"Squifflet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.K.C.","family":"Cooper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ph.","family":"Morel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2002,2,6]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-198711000-00026"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199607150-00028"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.34.11.1113"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.35.4.464"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.2337\/diab.38.1.S217"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.48.12.2340"},{"key":"e_1_2_7_8_2","first-page":"826","article-title":"Immunohistological study of islet xenograft rejection in immunosuppressed recipients","volume":"28","author":"ANDEREGGEN E","year":"1996","journal-title":"Transplant Proc"},{"key":"e_1_2_7_9_2","unstructured":"LEHNERTAM COWANP SALVARISEet\u2003al.High titre anti\u2010Gal antibodies cause islet graft rejection. 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Presented at the 25th Annual Scientific Meeting of the American Society of Transplant Surgeons Chicago USA 1999.","DOI":"10.1097\/00007890-199905150-00056"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3089.1995.tb00079.x"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200006150-00013"},{"key":"e_1_2_7_14_2","unstructured":"BUHLERL ALWAYNIPJ BASKERMet\u2003al.CD40\u2013CD154 pathway blockade requires host macrophages to induce humoral unresponsiveness to pig hematopoietic cells in baboons.Transplantation(in press)."},{"key":"e_1_2_7_15_2","unstructured":"BUHLERL YAMADAK KITAMURAHet\u2003al.Pig kidney transplantation in baboons: anti\u2010Gal IgM is associated with acute humoral xenograft rejection and disseminated intravascular coagulation.Transplantation(in press)."},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-199901150-00004"},{"key":"e_1_2_7_17_2","unstructured":"COOPERDKC YEY NIEKRASZM.Heart transplantation in primates. 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