Gao Dengke, Dai Pengxiu, Fan Zhixin, Wang Jinglu, Zhang Yihua
College of Veterinary Medicine, Northwest A&F University, Xianyang, China.
Cell Transplant. 2022 Jan-Dec;31:9636897221081483. doi: 10.1177/09636897221081483.
Adipose-derived mesenchymal stem cells (ADSCs) are ideal sources for the treatment of diabetes, and the differentiation of ADSCs into insulin-producing cells (IPCs) through transfection of exogenous regulatory genes has been studied in depth. The differentiation of ADSCs is strictly regulated by a variety of transcription factors such as , , , , and . However, whether these genes can coordinately regulate the differentiation of ADSCs into IPCs is still unknown. In this study, five multigene coexpressing adenovirus vectors (, , , , and ) were constructed, and then the stocks of the packaged adenoviruses were used to infect the canine ADSCs (cADSCs). Based on results of morphological observation, dithizone staining, sugar-stimulated insulin secretion test, cellular insulin immunofluorescence assays, and the detection of pancreatic β-cell development-related genes in the induced cells, the best induction combination () was identified after comparative screening. This study provides a theoretical reference and an experimental basis for further research on stem cell replacement therapy for diabetes.
脂肪来源的间充质干细胞（ADSCs）是治疗糖尿病的理想细胞来源，通过转染外源性调控基因将ADSCs诱导分化为胰岛素分泌细胞（IPCs）已得到深入研究。ADSCs的分化受到多种转录因子如 、 、 、 和 的严格调控。然而，这些基因是否能协同调控ADSCs向IPCs的分化仍不清楚。本研究构建了5种多基因共表达腺病毒载体（ 、 、 、 和 ），然后用包装好的腺病毒感染犬ADSCs（cADSCs）。基于形态学观察、双硫腙染色、糖刺激胰岛素分泌试验、细胞胰岛素免疫荧光检测以及诱导细胞中胰腺β细胞发育相关基因的检测结果，经比较筛选确定了最佳诱导组合（ ）。本研究为进一步开展糖尿病干细胞替代治疗研究提供了理论参考和实验依据。
