Lechner Andreas, Nolan Anna L, Blacken Robyn A, Habener Joel F
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Howard Hughes Medical Institute, Boston, MA, USA.
Biochem Biophys Res Commun. 2005 Feb 11;327(2):581-8. doi: 10.1016/j.bbrc.2004.12.043.
Cellular replacement therapy holds promise for the treatment of diabetes mellitus but donor tissue is severely limited. Therefore, we investigated whether insulin-secreting cells could be differentiated in vitro from a monolayer of cells expanded from human donor pancreatic islets. We describe a three-step culture protocol that allows for the efficient generation of insulin-producing cell clusters from in vitro expanded, hormone-negative cells. These clusters express insulin at levels of up to 34% that of average freshly isolated human islets and secrete C-peptide upon membrane depolarization. They also contain cells expressing the other major islet hormones (glucagon, somatostatin, and pancreatic polypeptide). The source of the newly differentiated endocrine cells could either be indigenous stem/progenitor cells or the proliferation-associated dedifferentiation and subsequent redifferentiation of mature endocrine cells. The in vitro generated cell clusters may be efficacious in providing islet-like tissue for transplantation into diabetic recipients.
细胞替代疗法有望用于治疗糖尿病，但供体组织严重受限。因此，我们研究了能否从人供体胰岛扩增的单层细胞中体外分化出胰岛素分泌细胞。我们描述了一种三步培养方案，该方案可从体外扩增的、激素阴性的细胞中高效生成胰岛素产生细胞簇。这些细胞簇表达的胰岛素水平高达新鲜分离的人胰岛平均水平的34%，并在膜去极化时分泌C肽。它们还含有表达其他主要胰岛激素（胰高血糖素、生长抑素和胰多肽）的细胞。新分化的内分泌细胞的来源可能是内源性干/祖细胞，也可能是成熟内分泌细胞增殖相关的去分化及随后的再分化。体外生成的细胞簇可能有效地为糖尿病受体提供类似胰岛的组织用于移植。
