| Differential Outcomes in Pre-diabetic vs. Overtly Diabetic NOD Mice Nonmyeloablatively Conditioned with Co-stimulatory Blockade. | |
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MedLine Citation:
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PMID: 21726515 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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OBJECTIVE: Autoimmune diabetes can be reversed with mixed chimerism. However, the myelotoxic agents currently required to establish chimerism have prevented the translation of this approach to the clinic. Here, we investigated whether multimodal co-stimulatory blockade would enhance chimerism and promote islet allograft tolerance in spontaneously diabetic NOD mice METHODS: Pre-diabetic and spontaneously diabetic NOD mice were preconditioned with anti-CD8 monoclonal antibody (mAb) prior to conditioning with 500 cGy total body irradiation and transplantation with 30 x 10(6) B10.BR bone marrow cells. Overtly diabetic animals were conditioned similarly and transplanted with 300-400 B10.BR islets. After irradiation, both groups of recipients were treated with anti-CD154, anti-OX40L, and anti-ICOS mAbs. Urine, blood glucose levels, and chimerism were monitored RESULTS: Conditioning of non-obese diabetic (NOD) mice with co-stimulatory blockade significantly enhanced engraftment, with 61% of mice engrafting at 1 month. Eleven of twelve chimeric animals with engraftment at 1 month remained diabetes-free over a 12 month follow-up, whereas non-chimeric animals progressed to diabetes. In contrast, similar conditioning prolonged islet allograft survival in only 2 of 11 overtly diabetic NOD recipients. Chimerism levels in the 9 islet rejector animals were 0%. CONCLUSION: Although nonmyeloablative conditioning reversed the autoimmune process in pre-diabetic NOD mice, the same regimen was significantly less effective in establishing chimerism and reversing autoimmune diabetes in spontaneously diabetic NOD mice. |
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Authors:
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Larry D Bozulic; Yiming Huang; Hong Xu; Yujie Wen; Suzanne T Ildstad |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-1 |
Journal Detail:
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Title: Experimental hematology Volume: - ISSN: 1873-2399 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-7-5 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0402313 Medline TA: Exp Hematol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved. |
Affiliation:
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Employee of Regenerex, LLC, 333 East Main Street, Suite 400, Louisville, KY 40202. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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