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https://hdl.handle.net/2440/121151
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dc.contributor.author | Stokes, R.A. | - |
dc.contributor.author | Cheng, K. | - |
dc.contributor.author | Deters, N. | - |
dc.contributor.author | Lau, S.M. | - |
dc.contributor.author | Hawthorne, W.J. | - |
dc.contributor.author | O'Connell, P.J. | - |
dc.contributor.author | Stolp, J. | - |
dc.contributor.author | Grey, S. | - |
dc.contributor.author | Loudovaris, T. | - |
dc.contributor.author | Kay, T.W. | - |
dc.contributor.author | Thomas, H.E. | - |
dc.contributor.author | Gonzalez, F.J. | - |
dc.contributor.author | Gunton, J.E. | - |
dc.date.issued | 2013 | - |
dc.identifier.citation | Cell Transplantation, 2013; 22(2):259-266 | - |
dc.identifier.issn | 0963-6897 | - |
dc.identifier.issn | 1555-3892 | - |
dc.identifier.uri | http://hdl.handle.net/2440/121151 | - |
dc.description.abstract | A high proportion of β-cells die within days of islet transplantation. Reports suggest that induction of hypoxia-inducible factor-1α (HIF-1α) predicts adverse transplant outcomes. We hypothesized that this was a compensatory response and that HIF-1α protects β-cells during transplantation. Transplants were performed using human islets or murine β-cell-specific HIF-1α-null (β-HIF-1α-null) islets with or without treatment with deferoxamine (DFO) to increase HIF-1α. β-HIF-1α-null transplants had poor outcomes, demonstrating that lack of HIF-1α impaired transplant efficiency. Increasing HIF-1α improved outcomes for mouse and human islets. No effect was seen in β-HIF-1α-null islets. The mechanism was decreased apoptosis, resulting in increased β-cell mass posttransplantation. These findings show that HIF-1α is a protective factor and is required for successful islet transplant outcomes. Iron chelation with DFO markedly improved transplant success in a HIF-1α-dependent manner, thus demonstrating the mechanism of action. DFO, approved for human use, may have a therapeutic role in the setting of human islet transplantation. | - |
dc.description.statementofresponsibility | Rebecca A. Stokes, Kim Cheng, Natasha Deters, Sue Mei Lau, Wayne J. Hawthorne ... Shane Grey ... et al. | - |
dc.language.iso | en | - |
dc.publisher | SAGE Publications | - |
dc.rights | © 2013 Cognizant Comm. Corp. | - |
dc.source.uri | http://dx.doi.org/10.3727/096368912x647180 | - |
dc.subject | Hypoxia-inducible factor-1α (HIF-1α), β-Cell function, islet transplantation; deferoxamine (DFO); diabetes; hypoxia | - |
dc.title | Hypoxia-inducible factor-1α (HIF-1α) potentiates β-cell survival after islet transplantation of human and mouse islets | - |
dc.title.alternative | Hypoxia-inducible factor-1alpha (HIF-1alpha) potentiates beta-cell survival after islet transplantation of human and mouse islets | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.3727/096368912X647180 | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Grey, S. [0000-0003-2160-1625] | - |
Appears in Collections: | Animal and Veterinary Sciences publications Aurora harvest 8 |
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