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EMBO reports 7, 4, 438–443 (2006)
doi:10.1038/sj.embor.7400640
AOP Published online: 10 February 2006
Inhibition of apoptosis by survivin improves transplantation of pancreatic islets for treatment of diabetes in mice
Takehiko Dohi1, Whitney Salz1, Marco Costa2, Charlotte Ariyan3, Giacomo P Basadonna2, 4 & Dario C Altieri1, 4
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1 Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
2 Department of Surgery, University of Massachusetts Medical School, 364 Plantation Street, Worcester, Massachusetts 01605, USA
3 Department of Surgery, Yale University School of Medicine, 330 Cedar Street, New Haven, Connecticut 06520, USA
4 These authors contributed equally to this work
To whom correspondence should be addressed
Dario C Altieri Tel: +1 508 856 5775; Fax: +1 508 856 5792; E-mail: dario.altieri@umassmed.edu
Received 17 October 2005; Accepted 17 January 2006; Published online 10 February 2006.
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Abstract
Survivin is a cancer gene implicated in inhibition of apoptosis and regulation of mitosis, but its function in normal cells has remained elusive. Here, we show that transgenic mice expressing survivin in pancreatic islet  -cells show no changes in cell proliferation, as determined by islet size or islet number. Transplantation of survivin transgenic islets in diabetic recipient mice affords long-term engraftment and stable correction of hyperglycaemia. This involves intrinsic inhibition of -cell apoptosis, in vivo, and global transcriptional changes in pancreatic islets with upregulation of stress response genes, antagonists of cytokine signalling and promoters of angiogenesis. These broad cytoprotective functions of survivin in vivo might be beneficial for gene therapy of diabetes.
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