San Raffaele Diabetes Research Institute, San Raffaele Scientific Institute, 20132 Milan, Italy.
Stem Cells. 2010 Jan;28(1):140-51. doi: 10.1002/stem.259.
Adherent fibroblast-like cells have been reported to appear in cultures of human endocrine or exocrine pancreatic tissue during attempts to differentiate human beta cells from pancreatic precursors. A thorough characterization of these mesenchymal cells has not yet been completed, and there are no conclusive data about their origin.We demonstrated that the human mesenchymal cells outgrowing from cultured human pancreatic endocrine or exocrine tissue are pancreatic mesenchymal stem cells (pMSC) that propagate from contaminating pMSC. The origin of pMSC is partly extrapancreatic both in humans and mice, and by using green fluorescent protein (GFP(+)) bone marrow transplantation in the mouse model, we were able to demonstrate that these cells derive from the CD45(+) component of bone marrow. The pMSC express negligible levels of islet-specific genes both in basal conditions and after serum deprivation or exogenous growth factor exposure, and might not represent optimal candidates for generation of physiologically competent beta-cells. On the other hand, when cotransplanted with a minimal pancreatic islet mass, pMSC facilitate the restoration of normoglycemia and the neovascularization of the graft. These results suggest that pMSCs could exert an indirect role of "helper" cells in tissue repair processes.
在试图从人胰腺前体细胞中分化人胰岛β细胞的过程中，有报道称黏附成纤维样细胞出现在人内分泌或外分泌胰腺组织的培养物中。这些间充质细胞尚未得到充分的特征描述，其来源也没有确凿的数据。我们证明，从培养的人胰腺内分泌或外分泌组织中长出的人间质细胞是胰腺间充质干细胞（pMSC），它们来源于污染的 pMSC。在人和小鼠中，pMSC 的部分来源是胰外的，并且通过在小鼠模型中使用绿色荧光蛋白（GFP(+））骨髓移植，我们能够证明这些细胞来自骨髓的 CD45(+)成分。pMSC 在基础条件下以及在血清剥夺或外源性生长因子暴露后，表达的胰岛特异性基因水平可忽略不计，可能不是生成具有生理功能的β细胞的最佳候选细胞。另一方面，当与最小量的胰岛一起共移植时，pMSC 有助于恢复正常血糖水平和移植物的新生血管化。这些结果表明，pMSC 可以在组织修复过程中发挥“辅助”细胞的间接作用。
