Department of Molecular Cell Biology, Leiden University Medical Center, Leiden, The Netherlands.
Islets. 2010 May-Jun;2(3):164-73. doi: 10.4161/isl.2.3.11449.
Islet replacement is a promising approach for type-1 diabetes treatment, but the shortage of organ donors demands new sources of β-cells. The use of stem/precursor cells may represent an attractive alternative. Islet-derived stem/precursor cells (hIPC) have been isolated from human islet preparations, but neither their origin, nor their contribution to β-cell formation in the adult pancreas, are well understood. To study these cells in more detail hIPC were isolated from purified human islets, cultured and functionally characterized. Cultured hIPC did not express the genes for endocrine hormones. These cells exhibited the capacity to aggregate and form clusters when transferred to serum-free medium. In these clusters the expression of insulin, glucagon, and somatostatin genes is induced. Human IPC lack expression of Von Willebrand Factor, CD31, CD34, CD45, and CK19 and CA19.9, demonstrating that hIPC are neither of hematopoietic, endothelial, nor of ductal origin. The mesenchymal stem cells (MSC) markers CD105, CD90, CD73, CD44, CD29, and CD13 are expressed, as well as nestin and vimentin. With the appropriate stimuli the cells can differentiate into adipocytes and osteoblasts lineages. Also hIPC express the pericyte markers CD146, NG2, αSMA and PDGF-Rβ. Immunoflowcytometry revealed that human islets contain 2.0 ± 0.8% of CD105/CD90 double-positive cells. Confocal microscopy showed that these cells reside within the human islets. Altogether our data revealed the presence of a distinct MSC-like stem cell population in isolated human islets.
胰岛细胞替代是治疗 1 型糖尿病的一种很有前途的方法，但器官捐献者的短缺要求寻找新的β细胞来源。干细胞/前体细胞的应用可能是一种有吸引力的替代方法。已经从人胰岛制剂中分离出胰岛衍生的干细胞/前体细胞（hIPC），但其起源及其在成人胰腺中形成β细胞的作用尚不清楚。为了更详细地研究这些细胞，从纯化的人胰岛中分离出 hIPC 并进行培养和功能表征。培养的 hIPC 不表达内分泌激素的基因。当这些细胞被转移到无血清培养基中时，它们具有聚集和形成簇的能力。在这些簇中，胰岛素、胰高血糖素和生长抑素基因的表达被诱导。人 IPC 缺乏血管性血友病因子、CD31、CD34、CD45 和 CK19 和 CA19.9 的表达，表明 hIPC 既不是造血细胞、内皮细胞，也不是导管细胞。间充质干细胞（MSC）标志物 CD105、CD90、CD73、CD44、CD29 和 CD13 以及巢蛋白和波形蛋白的表达，以及细胞可以分化为脂肪细胞和成骨细胞谱系。此外，hIPC 还表达周细胞标志物 CD146、NG2、αSMA 和 PDGF-Rβ。免疫荧光显示，人胰岛中含有 2.0±0.8%的 CD105/CD90 双阳性细胞。共聚焦显微镜显示这些细胞位于人胰岛内。总的来说，我们的数据显示在分离的人胰岛中存在一种独特的 MSC 样干细胞群体。
