Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation

Y. Clare Zhang, R. Damaris Milano, Antonello Pileggi, Matthew Powers, Jeffrey Cross, Clive Wasserfall, Marda Scott-Jorgensen, Martha Campbell-Thompson, James M. Crawford, Terence Flotte, Tamir M. Ellis, Camillo Ricordi, Mark A. Atkinson, Luca Inverardi

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Abstract

Previous studies suggest that therapeutic expression of interleukin (IL)-4 by islet cells improves their efficacy in transplantation models directed at reversing type 1 diabetes. We investigated the effects of introducing IL-4 into islets with recombinant adenoassociated virus (rAAV) on the reversal of hyperglycemia in a syngeneic marginal islet mass transplantation model. C57BL/6 islets were mock-transduced or transduced with rAAV expressing murine IL-4 (rAAV-IL-4) or rAAV expressing green fluorescent protein (rAAV-GFP) before transplantation of a marginal mass into diabetic mice. Normoglycemia was achieved in only 1/7 mice receiving rAAV-IL-4 transduced islets in comparison to 6/6 mock-transduced and 4/6 rAAV-GFP transduced animals. The failure of IL-4 expressing islets was not associated with cellular toxicity of rAAV or impairment of glucose-stimulated insulin release in vitro. Islet expression of IL-4 led to impaired metabolic function in mice receiving a marginal mass of syngeneic islets.

Original languageEnglish (US)
Pages (from-to)1184-1186
Number of pages3
JournalTransplantation
Volume74
Issue number8
DOIs
StatePublished - Oct 27 2002

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ASJC Scopus subject areas

  • Transplantation

Cite this

Zhang, Y. C., Milano, R. D., Pileggi, A., Powers, M., Cross, J., Wasserfall, C., Scott-Jorgensen, M., Campbell-Thompson, M., Crawford, J. M., Flotte, T., Ellis, T. M., Ricordi, C., Atkinson, M. A., & Inverardi, L. (2002). Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation. Transplantation, 74(8), 1184-1186. https://doi.org/10.1097/00007890-200210270-00022