人脂肪间充质干细胞诱导分化为表达胰岛素、生长抑素和胰高血糖素

                       的细胞

小鼠骨髓间充质干细胞在体外表达胰脏内分泌物的表型，能治愈糖尿病的动物模型。来自人脂肪组织的间充质干细胞与骨髓间充质干细胞是一类具有非常相似表型的细胞群。脂肪组织来源充足，取材容易而且包含胰岛素前体细胞。我们从四个健康的供体分离人脂肪间充质干细胞。细胞增殖期间表达表达nestin 、ABCG2、SCF、Thy-1干细胞表面标志和胰脏内分泌物转录因子Isl-1。分离的细胞通过特定培养基培养三天诱导分化为表达胰脏内分泌物表型的细胞。当向胰岛素、生长抑素和胰高血糖素的细胞诱导时，定量PCR检测观察到ABCG2 下调,胰脏发育转录因子Isl-1、Ipf-1、Ngn3上调。

   Human adipose tissue-derived mesenchymal stem cells differentiate  into insulin, somatostatin, and glucagon expressing cells

Katharina Timper ^a,1, Dalma Seboek ^a,1, Michael Eberhardt ^a, Philippe Linscheid ^a,Mirjam Christ-Crain ^b, Ulrich Keller ^a,b, Beat Mu¨ ller ^a,b, Henryk Zulewski ^a,b,*

                                       ^a Department of Research, University Hospital, Basel, Switzerland                                                                                                        ^b Division of Endocrinology, Diabetes and Clinical Nutrition, University Hospital, Basel, Switzerland

Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.