| Rapamycin does not adversely affect intrahepatic islet engraftment in mice and improves early islet engraftment in humans. | |
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MedLine Citation:
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PMID: 21084848 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: In this study we examined the effect of rapamycin (RAPA), a key component of the immunosuppressive regimen in clinical islet transplantation, on islet engraftment and function in vivo. METHODS AND RESULTS: Diabetic C57BL/6 or BALB/C recipient mice were transplanted with 350 syngeneic islets through the portal vein (PV-Tx; C57BL/6 n = 60; BALB/C n = 22) and treated with once-daily oral RAPA (1 mg/kg) or vehicle. No differences in post-transplant blood glucose concentrations and glucose tolerance were observed between RAPA- and vehicle-treated mice. The impact of RAPA on human islet engraftment was assessed in 10 patients with type 1 diabetes treated with : 0.1 mg/kg/day rapamycin before islet transplantation. Compared to non pre-treated islet transplant recipients (n = 12), RAPA pre-treated patients had increased blood RAPA concentrations (p = 0.006) and fasting C-peptide concentrations (p = 0.005) in the two weeks post-transplant. RAPA pre-treatment was associated with a reduction in chemokines CCL2 and CCL3 concentrations pre-transplant (p < 0.01), and a dampened chemokine response (p = 0.005) post-transplant. Concordantly, in vitro RAPA inhibited the secretion of CCL2 and CCL3 by monocytes. CONCLUSION: Rapamycin does not adversely affect intrahepatic islet engraftment in the mouse, and potentially improves islet engraftment in humans by an anti-inflammatory mechanism. |
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Authors:
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Raffaella Melzi; Paola Maffi; Rita Nano; Valeria Sordi; Alessia Mercalli; Marina Scavini; Antonio Secchi; Ezio Bonifacio; Lorenzo Piemonti |
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Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Islets Volume: 1 ISSN: 1938-2022 ISO Abbreviation: Islets Publication Date: 2009 Jul-Aug |
Date Detail:
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Created Date: 2010-11-18 Completed Date: 2011-03-31 Revised Date: 2011-11-24 |
Medline Journal Info:
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Nlm Unique ID: 101495366 Medline TA: Islets Country: United States |
Other Details:
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Languages: eng Pagination: 42-9 Citation Subset: IM |
Affiliation:
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Beta Cell Biology Unit, San Raffaele Diabetes Research Institute (HSR-DRI), San Raffaele Scientific Institute, Milan, Italy. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Animals Drug Evaluation, Preclinical Female Graft Survival / drug effects* Humans Immunosuppressive Agents / pharmacology Islets of Langerhans Transplantation / methods* Liver Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Sirolimus / pharmacology* Species Specificity Time Factors Transplantation, Heterotopic / methods* |
| Grant Support | |
ID/Acronym/Agency:
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JT01Y01//Telethon |
| Chemical | |
Reg. No./Substance:
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0/Immunosuppressive Agents; 53123-88-9/Sirolimus |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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