Department of Animal Genetic Resources, Chinese Academy of Agricultural Sciences, Beijing, China.
From the Department of Kinesiology, University of Shanghai Sport, Shanghai.
Pancreas. 2020 Aug;49(7):947-954. doi: 10.1097/MPA.0000000000001604.
This study aims to investigate the characteristics of sheep pancreatic mesenchymal stem cells (PSCs) and therapeutic potential of differentiated β-like cells in streptozotocin-induced diabetic mice.
Pancreatic mesenchymal stem cells were isolated from 3- to 4-month-old sheep embryos, and their biological characteristics were explored. The function and therapeutic potential of differentiated β-like insulin-producing cells were also investigated in vitro and in vivo. Differentiated cells were identified through dithizone staining and immunofluorescence staining. Insulin secretion was analyzed using an enzyme-linked immunosorbent assay kit. The preliminary therapeutic potential of induced β-like cells in diabetic mice was detected by blood glucose and body weight.
Primary PSCs were isolated and subcultured up to passage 36. Immunofluorescence staining presented PSC-expressed important markers such as Pdx1, Nkx6-1, Ngn3, and Nestin. Primary PSCs could be induced into functional pancreatic β-like islet cells with a 3-step protocol. The induced β-like islet cells could ameliorate blood glucose in diabetic mice.
The method proposed for generating pancreatic islet β cells provided a preliminary phenotypic investigation of induced cell treatment in diabetic mice, and also laid a foundation in the identification of pharmaceutical targets to treat insulin-dependent diabetes.
本研究旨在探讨绵羊胰腺间充质干细胞（PSCs）的特征，以及分化的β样细胞在链脲佐菌素诱导的糖尿病小鼠中的治疗潜力。
从 3 至 4 月龄绵羊胚胎中分离胰腺间充质干细胞，并探索其生物学特性。还在体外和体内研究了分化的β样胰岛素分泌细胞的功能和治疗潜力。通过二硫腙染色和免疫荧光染色鉴定分化细胞。使用酶联免疫吸附试剂盒分析胰岛素分泌。通过血糖和体重检测诱导的β样细胞在糖尿病小鼠中的初步治疗潜力。
成功分离和传代培养了原代 PSCs，可达 36 代。免疫荧光染色显示 PSCs 表达重要标志物，如 Pdx1、Nkx6-1、Ngn3 和 Nestin。通过 3 步方案可将原代 PSCs 诱导为功能性胰腺β样胰岛细胞。诱导的β样胰岛细胞可改善糖尿病小鼠的血糖水平。
所提出的生成胰岛β细胞的方法为诱导细胞治疗糖尿病小鼠提供了初步的表型研究，并为治疗胰岛素依赖型糖尿病的药物靶点鉴定奠定了基础。
