Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation.
Adeno-associated virus transduction of islets with interleukin-4 results in impaired metabolic function in syngeneic marginal islet mass transplantation.
复制标题
腺相关病毒用白细胞介素 4 转导胰岛，导致同基因边缘胰岛大量移植中代谢功能受损。
作者：
Y. C. Zhang;R. Molano;A. Pileggi;Matthew Powers;Jeff Cross;C. Wasserfall;Marda Scott;M. Campbell;James M. Crawford;T. Flotte;T. Ellis;C. Ricordi;M. Atkinson;L. Inverardi
先前的研究表明，胰岛细胞治疗性表达白细胞介素(IL)-4可提高其在移植模型中逆转1型糖尿病的疗效。我们研究了用重组腺相关病毒（rAAV）将IL-4引入胰岛后在同基因边缘胰岛移植模型中逆转高血糖的作用。在将C57BL/6胰岛移植到糖尿病小鼠体内之前，分别用表达小鼠IL-4 （rAAV-IL-4）或表达绿色荧光蛋白（rAAV- gfp）的rAAV模拟或转导C57BL/6胰岛。接受rAAV-IL-4转导胰岛的小鼠中，只有1/7实现了正常血糖，而接受rAAV-IL-4转导胰岛的小鼠为6/6，接受rAAV-GFP转导的小鼠为4/6。在体外实验中，IL-4表达胰岛的失败与rAAV的细胞毒性或葡萄糖刺激的胰岛素释放损伤无关。胰岛IL-4的表达导致接受少量同基因胰岛的小鼠代谢功能受损。
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.
使用双顺反子重组腺相关病毒载体转导人和小鼠胰岛细胞。
DOI：
10.1006/mthe.2002.0522
发表时间：
2002
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
影响因子：
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作者：
Kapturczak,Matthias;Zolotukhin,Sergei;Cross,Jeff;Pileggi,Antonello;Molano,RDamaris;Jorgensen,Marda;Byrne,Barry;Flotte,TerenceR;Ellis,Tamir;Inverardi,Luca;Ricordi,Camillo;Nick,Harry;Atkinson,Mark;Agarwal,Anupam
通讯作者：
Agarwal,Anupam