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Deducing Insulin-Producing Cells from Goat Adipose Tissue-Derived Mesenchymal Stem Cells
Cellular Reprogramming ( IF 1.6 ) Pub Date : 2022-08-12 , DOI: 10.1089/cell.2022.0029
Amit Dubey 1 , Sikander Saini 1 , Vishal Sharma 1 , Hrudananda Malik 1 , Dinesh Kumar 1 , Arun Kumar De 2 , Debasis Bhattacharya 2 , Dhruba Malakar 1
Affiliation  

Mesenchymal stem cell is a potent tool for regenerative medicine against control of incurable diseases in human and animals. Diabetes mellitus is one such condition marked with the blood glucose is high due to lack of insulin (INS) hormone secreted by the pancreatic cells. Rare, but sporadic, cases of dysfunctional pancreatic cells in goat as well as the promises of stem cell therapy as an off-the-shelf medicine prompted us to explore the potential of adipose-derived goat mesenchymal stem cells (AD-MSCs) to transdifferentiate into pancreatic islet-like cells. We isolated, in vitro cultured, and characterized the AD-MSCs by expression of MSC-specific markers and differentiation into multiple mesodermal lineage cells. The characterized AD-MSCs were in vitro transdifferentiated into INS-producing islet-like cells using a cocktail of glucose, nicotinamide, activin-A, exendin-4, pentagastrin, retinoic acid, and mercaptoethanol in 3 weeks. The transdifferentiated islet-like cells demonstrated the expression of pancreatic endoderm-specific transcripts PDX1, NGN3, PAX6, PAX4, ISL1, and GLUT2 as well as protein expression of pancreatic and duodenal homeobox 1 (PDX1), INS, and Islets 1 (ISL1). The islet-like cells also demonstrated the significant glucose-dependent INS release with respect to the course of transdifferentiation regime. The study envisaged to create the building material for basic research into mechanism of glucose homeostasis, which may pave road for developments in diabetes drug discovery and regenerative therapies.

中文翻译:

从山羊脂肪组织来源的间充质干细胞中推导产生胰岛素的细胞

间充质干细胞是一种有效的再生医学工具,可用于控制人类和动物的不治之症。由于胰腺细胞分泌的胰岛素(INS)激素缺乏,糖尿病是一种以血糖高为标志的疾病。山羊胰腺细胞功能失调的罕见但零星病例以及干细胞治疗作为现成药物的前景促使我们探索脂肪来源的山羊间充质干细胞 (AD-MSCs) 转分化的潜力进入胰岛样细胞。我们通过表达 MSC 特异性标志物和分化成多个中胚层谱系细胞来分离、体外培养和表征 AD-MSC。表征的 AD-MSCs在体外使用葡萄糖、烟酰胺、激活素 A、exendin-4、五胃泌素、视黄酸和巯基乙醇的混合物在 3 周内转分化为产生 INS 的胰岛样细胞。转分化的胰岛样细胞表现出胰腺内胚层特异性转录物PDX1NGN3PAX6PAX4ISL1GLUT2的表达以及胰腺和十二指肠同源框 1 (PDX1)、INS 和胰岛 1 (ISL1) 的蛋白质表达。胰岛样细胞在转分化过程中也表现出显着的葡萄糖依赖性 INS 释放。该研究旨在为葡萄糖稳态机制的基础研究创造基础材料,这可能为糖尿病药物发现和再生疗法的发展铺平道路。
更新日期:2022-08-16
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