Abstract
Encapsulated islet cells have potential for use in cellular therapy for type I diabetes, but cell survival under hypoxia during revascularization is a serious problem lessening the effect of cellular therapy. To overcome the difficulty in cell survival under hypoxia, we have introduced the anti-apoptotic genes, crmA and bcl-2, into a RIN-5F cell line derived from rat islet of Langerhans cells, named RIN-5F-CrmA and RIN-5F-Bcl-2, respectively. RT-PCR and immunoblotting showed that RIN-5F-CrmA cells stably expressed crmA transcripts and that RIN-5F-Bcl-2 cells stably expressed Bcl-2, respectively. Over-expression of these anti-apoptotic genes prolonged the culture period under hypoxic conditions ( pO 2 2%). In hypoxia, Rin-5F cell lines produced less insulin, but over-expression of crmA significantly reduced the decrease of insulin synthesis in hypoxic culture. These results indicate that both CrmA and Bcl-2 are effective for inhibiting cell death under hypoxia, and suggest that CrmA would be superior to Bcl-2 because of the improved insulin production in hypoxia. This anti-apoptotic approach would have important therapeutic implications for successful transplantation of encapsulated islet cells.
Published Version
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