Liu Hui-Yu, Chen Chih-Chien, Lin Yuan-Yu, Chen Yu-Jen, Liu Bing-Hsien, Wong Shiu-Chung, Wu Cheng-Yu, Chang Yun-Tsui, Chou Han-Yi E, Ding Shih-Torng
Department of Animal Science and Technology, National Taiwan University, Taipei City, Taiwan, R.O.C.
Institute of Biotechnology, National Taiwan University, Taipei City, Taiwan.
PLoS One. 2017 Mar 2;12(3):e0172922. doi: 10.1371/journal.pone.0172922. eCollection 2017.
The unique advantage of easy access and abundance make the adipose-derived stem cells (ADSCs) a promising system of multipotent cells for transplantation and regenerative medicine. Among the available sources, porcine ADSCs (pADSCs) deserve especial attention due to the close resemblance of human and porcine physiology, as well as for the upcoming availability of humanized porcine models. Here, we report on the isolation and conversion of pADSCs into glucose-responsive insulin-secreting cells. We used the stromal-vascular fraction of the dorsal subcutaneous adipose from 9-day-old male piglets to isolate pADSCs, and subjected the cells to an induction scheme for differentiation on chitosan-coated plates. This one-step procedure promoted differentiation of pADSCs into pancreatic islet-like clusters (PILC) that are characterized by the expression of a repertoire of pancreatic proteins, including pancreatic and duodenal homeobox (Pdx-1), insulin gene enhancer protein (ISL-1) and insulin. Upon glucose challenge, these PILC secreted high amounts of insulin in a dose-dependent manner. Our data also suggest that chitosan plays roles not only to enhance the differentiation potential of pADSCs, but also to increase the glucose responsiveness of PILCs. Our novel approach is, therefore, of great potential for transplantation-based amelioration of type 1 diabetes.
易于获取和数量丰富这一独特优势，使脂肪来源干细胞（ADSCs）成为用于移植和再生医学的多能细胞的一个有前景的体系。在现有的细胞来源中，猪脂肪来源干细胞（pADSCs）值得特别关注，这是因为猪与人的生理机能极为相似，而且人源化猪模型即将问世。在此，我们报告了pADSCs的分离以及将其转化为葡萄糖反应性胰岛素分泌细胞的过程。我们利用9日龄雄性仔猪背部皮下脂肪的基质血管成分来分离pADSCs，并将这些细胞置于壳聚糖包被的培养板上进行诱导分化。这一步骤促使pADSCs分化为胰岛样细胞簇（PILC），其特征是表达一系列胰腺蛋白，包括胰腺十二指肠同源框蛋白（Pdx-1）、胰岛素基因增强子蛋白（ISL-1）和胰岛素。在葡萄糖刺激下，这些PILC以剂量依赖的方式分泌大量胰岛素。我们的数据还表明，壳聚糖不仅在增强pADSCs的分化潜能方面发挥作用，而且还能提高PILC的葡萄糖反应性。因此，我们的新方法对于基于移植改善1型糖尿病具有巨大潜力。
