Zhang Y Clare, Molano R Damaris, Pileggi Antonello, Powers Matthew, Cross Jeffrey, Wasserfall Clive, Scott-Jorgensen Marda, Campbell-Thompson Martha, Crawford James M, Flotte Terence, Ellis Tamir M, Ricordi Camillo, Atkinson Mark A, Inverardi Luca
Department of Pathology, University of Florida, 1600 SW Archer Road, Gainesville, FL 32610, USA.
Transplantation. 2002 Oct 27;74(8):1184-6. doi: 10.1097/00007890-200210270-00022.
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 adeno-associated 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.
先前的研究表明，胰岛细胞对白介素（IL）-4进行治疗性表达可提高其在旨在逆转1型糖尿病的移植模型中的功效。我们研究了用重组腺相关病毒（rAAV）将IL-4导入胰岛对同基因边缘胰岛移植模型中高血糖逆转的影响。在将边缘胰岛移植到糖尿病小鼠体内之前，对C57BL/6胰岛进行空载转导或用表达小鼠IL-4的rAAV（rAAV-IL-4）或表达绿色荧光蛋白的rAAV（rAAV-GFP）进行转导。与6/6接受空载转导和4/6接受rAAV-GFP转导的动物相比，仅1/7接受rAAV-IL-4转导胰岛的小鼠实现了血糖正常。表达IL-4的胰岛移植失败与rAAV的细胞毒性或体外葡萄糖刺激的胰岛素释放受损无关。IL-4在胰岛中的表达导致接受同基因胰岛边缘移植的小鼠代谢功能受损。
