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Hypoxia-Inducible Factor-1α (HIF-1α) Potentiates β-Cell Survival after Islet Transplantation of Human and Mouse Islets
- Source :
- Cell Transplantation, Vol 22 (2013)
- Publication Year :
- 2013
- Publisher :
- SAGE Publishing, 2013.
-
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.
- Subjects :
- Medicine
Subjects
Details
- Language :
- English
- ISSN :
- 09636897 and 15553892
- Volume :
- 22
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Transplantation
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.bf393fb87b848a894f35f553d1e4133
- Document Type :
- article
- Full Text :
- https://doi.org/10.3727/096368912X647180