Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes
Adult bone marrow-derived cells trans-differentiating into insulin-producing cells for the treatment of type I diabetes
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DOI：
10.1038/labinvest.3700074
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发表时间：
2004-05-01
影响因子：
5
通讯作者：
Petersen, BE
中科院分区：
文献类型：
--
作者：
Oh, SH;Muzzonigro, TM;Petersen, BE
近期的研究结果表明，骨髓（BM）细胞具有分化为多种细胞类型的能力，包括胰腺的内分泌细胞。我们报道，在特定条件下培养时，骨髓来源的细胞可被诱导转分化为胰岛素生成细胞。此外，这些胰岛素生成细胞形成聚集体，将其移植到小鼠体内后，其结构类似于胰岛。这些聚集体显示出胰岛素（I和II）、胰高血糖素、生长抑素和胰多肽的内分泌基因表达。免疫组织化学也证实这些聚集体对胰岛素、生长抑素、胰多肽和C肽呈阳性。而且，蛋白质印迹和酶联免疫吸附测定分析表明，在葡萄糖刺激下，胰岛素原表达和/或活性胰岛素分泌。将这些聚集体肾被膜下移植到高血糖小鼠体内，可降低循环血糖水平，并在移植后长达90天内维持相对正常的血糖水平。移除移植物会导致实验动物迅速复发和死亡。此外，电子显微镜显示这些聚集体已获得通常与成熟β细胞相关的超微结构。这些结果表明，成年骨髓细胞能够在体外转分化为胰腺谱系，并可能代表一种用于治疗糖尿病的细胞库。
Recent findings suggest that bone marrow (BM) cells have the capacity to differentiate into a variety of cell types including endocrine cells of the pancreas. We report that BM derived cells, when cultured under defined conditions, were induced to trans-differentiate into insulin-producing cells. Furthermore, these insulin-producing cells formed aggregates that, upon transplantation into mice, acquired architecture similar to islets of Langerhans. These aggregates showed endocrine gene expression for insulin (I and II), glucagon, somatostatin and pancreatic polypeptide. Immunohistochemistry also confirmed that these aggregates were positive for insulin, somatostatin, pancreatic polypeptide and C-peptide. Also, Western and ELISA analysis demonstrated expression of proinsulin and/or secretion of active insulin upon glucose challenge. Subcapsular renal transplantation of these aggregates into hyperglycemic mice lowered circulating blood glucose levels and maintained comparatively normal glucose levels for up to 90 days post-transplantation. Graft removal resulted in rapid relapse and death in experimental animals. In addition, electron microscopy revealed these aggregates had acquired ultrastructure typically associated with mature beta (beta) cells. These results demonstrate that adult BM cells are capable of trans-differentiating into a pancreatic lineage in vitro and may represent a pool of cells for the treatment of diabetes mellitus.