Pig Embryonic Pancreatic Tissue as a Source for Transplantation

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Posted by Ellen on 10:52:37 2009/06/30

Your browser does not support inline frames, or it has been configured incorrectly. If page does not display on your browser, please <a href="http://diabetes.diabetesjournals.org/content/58/7/1585.abstract">CLICK HERE</a>. Pig Embryonic Pancreatic Tissue as a Source for Transplantation in Diabetes — Diabetes var callbackToken='57942C62DABDC14'; Skip to main page content Home Current Issue Archive Contact Subscribe Alerts Help Search GO Advanced Search » User Name Password Sign In Pig Embryonic Pancreatic Tissue as a Source for Transplantation in Diabetes Transient Treatment With Anti-LFA1, Anti-CD48, and FTY720 Enables Long-Term Graft Maintenance in Mice With Only Mild Ongoing Immunosuppression Dalit Tchorsh-Yutsis 1 , Gil Hecht 1 , Anna Aronovich 1 , Elias Shezen 1 , Yael Klionsky 1 , Chava Rosen 1 , Rivka Bitcover 1 , Smadar Eventov-Friedman 1 , Helena Katchman 1 , Sivan Cohen 1 , Orna Tal 1 , Oren Milstein 1 , Hideo Yagita 2 , Bruce R. Blazar 3 and Yair Reisner 1 1 Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; 2 Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan; 3 Cancer Center and Department of Pediatrics, Division of Pediatric Hematology/Oncology and Blood and Marrow Transplant, University of Minnesota, Minneapolis, Minnesota. Corresponding author: Yair Reisner, yair.reisner{at}weizmann.ac.il . D.T.-Y. and G.H. contributed equally to this work. Abstract OBJECTIVE Defining an optimal costimulatory blockade–based immune suppression protocol enabling engraftment and functional development of E42 pig embryonic pancreatic tissue in mice. RESEARCH DESIGN AND METHODS Considering that anti-CD40L was found to be thrombotic in humans, we sought to test alternative costimulatory blockade agents already in clinical use, including CTLA4-Ig, anti-LFA1, and anti-CD48. These agents were tested in conjunction with T-cell debulking by anti-CD4 and anti-CD8 antibodies or with conventional immunosuppressive drugs. Engraftment and functional development of E42 pig pancreatic tissue was monitored by immunohistology and by measuring pig insulin blood levels. RESULTS Fetal pig pancreatic tissue harvested at E42, or even as early as at E28, was fiercely rejected in C57BL/6 mice and in Lewis rats. A novel immune suppression comprising anti-LFA1, anti-CD48, and FTY720 afforded optimal growth and functional development. Cessation of treatment with anti-LFA1 and anti-CD48 at 3 months posttransplant did not lead to graft rejection, and graft maintenance could be achieved for >8 months with twice-weekly low-dose FTY720 treatment. These grafts exhibited normal morphology and were functional, as revealed by the high pig insulin blood levels in the transplanted mice and by the ability of the recipients to resist alloxan induced diabetes. CONCLUSIONS This novel protocol, comprising agents that simulate those approved for clinical use, offer an attractive approach for embryonic xenogeneic transplantation. Further studies in nonhuman primates are warranted. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received January 26, 2009. Accepted April 15, 2009. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See <a style="font-weight:normal" href="http://creativecommons.org/licenses/by-nc-nd/3.0/">http://creativecommons.org/licenses/by-nc-nd/3.0/</a> for details. © 2009 by the American Diabetes Association. CiteULike Del.icio.us Digg Reddit Technorati Facebook Twitter What's this? « Previous | Next Article » Table of Contents This Article Published online before print April 28, 2009 , doi: 10.2337/db09-0112 Diabetes July 2009 vol. 58 no. 7 1585-1594 » Abstract Full Text Full Text (PDF) All Versions of this Article: db09-0112v1 58/7/1585 most recent Purchase Article View Shopping Cart Services Email this article to a colleague Alert me when this article is cited Alert me if a correction is posted Similar articles in this journal Similar articles in PubMed Download to citation manager Load patient INFORMation Citing Articles Load citing article information Google Scholar Articles by Tchorsh-Yutsis, D. Articles by Reisner, Y. PubMed PubMed citation Articles by Tchorsh-Yutsis, D. Articles by Reisner, Y. Social Bookmarking CiteULike Del.icio.us Digg Reddit Technorati Facebook Twitter What's this? Current Issue July 2009, 58 (7) Alert me to new issues of Diabetes Instructions for Authors Manuscript Submissions About the Journal Editorial Board Subscriptions PDA Services Advertising & Reprints ADA's DiabetesPro ADA Member Directory RSS Feeds E-mail Alerts Diabetes Care Clinical Diabetes Diabetes Spectrum Copyright © 2009 by the American Diabetes Association Print ISSN: 0012-1797 Online ISSN: 1939-327X var gaJsHost = (("https:" == document.location.protocol) ? "https://ssl." : "http://www."); document.write(unescape("%3Cscript src='" + gaJsHost + "google-analytics.com/ga.js' type='text/javascript'%3E%3C/script%3E")); var pageTracker = _gat._getTracker("UA-1543923-1"); pageTracker._trackPageview();

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