HUMAN BONE MARROW CONTRIBUTES TO ISLET REGNERATION IN VITRO

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。I型糖尿病的特征在于胰腺中产生胰岛素的胰岛细胞的破坏，导致高血糖症和相关的发病率。为探讨人骨髓细胞（BMC）体外诱导分化为胰岛样细胞的可能性，并检测其对糖尿病的治疗作用，本研究将GFP标记的小鼠BMC与胰腺共培养。发现小鼠BMC能够聚集形成胰岛样簇（用胰岛素原免疫组织化学鉴定）。这些发现使我们能够提出人BMC转分化为胰岛素产生细胞的可能性。在该试验性提案中，假设人BMC能够在某些情况下分化为胰岛素产生细胞，从而导致体内葡萄糖的调节。为了验证这一假设，首先，优化人BMC的培养基，使其分化为新的功能性胰岛素产生细胞将是必要的，并且沿着测试BMC是否能够在体外修复受损的胰岛;其次，将评估胰岛素产生细胞在基因和蛋白质水平上的特异性标志物的表达。此后，将胰岛样簇植入非肥胖糖尿病严重联合免疫缺陷（NOD-SCID）小鼠中，将测试这些骨髓来源的胰岛样产生簇的植入和功能。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Type I diabetes is characterized by the destruction of insulin-producing beta-islet cells in the pancreas, resulting in hyperglycemia and associated morbidity. To explore the possibility of human bone marrow cells (BMC) in vitro differentiating into functional islet-like cells and to test the diabetic therapeutic potency of islet-like cells, GFP positive labeled mice BMC was co-culture with the pancreas in our preliminary studies. It was found that mice BMC are able to aggregate in forming islet like clusters (identified with proinsulin immunohistochemistry). The findings enable us to propose the possibility of human BMC transdifferentiating into insulin producing cells. In this pilot proposal, it is hypothesized that human BMC is able to differentiate into insulin producing cells under certain circumstances, leading to the regulation of glucose in vivo. To test this hypothesis, first, the optimization of the medium for human BMC allowing the differentiation to new functional insulin producing cells will be necessary and along with testing whether BMC will be able to repair damaged islets in vitro; second, the expression of the specific markers for insulin producing cell in gene and protein levels will be evaluated. Thereafter, implantation of the islet like cluster into a non-obese diabetic severe combined immunodeficient (NOD-SCID) mice will test the engraftment and function of these bone marrow derived islet like producing clusters.