Department of Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China.
Cell Biol Int. 2011 May;35(5):483-90. doi: 10.1042/CBI20100152.
Stem/progenitor cells hold promise for alleviating/curing type 1 diabetes due to the capacity to differentiate into functional insulin-producing cells. The current study aims to assess the differentiation potential of human pancreatic IPCs (islet-derived progenitor cells). IPCs were derived from four human donors and subjected to more than 2000-fold expansion before turning into ICCs (islet-like cell clusters). The ICCs expressed ISL-1 Glut2, PDX-1, ngn3, insulin, glucagon and somatostatin at the mRNA level and stained positive for insulin and glucagon by immunofluorescence. Following glucose challenge in vitro, C-peptide was detected in the sonicated ICCs, instead of in the conditioned medium. To examine the function of the cells in vivo, IPCs or ICCs were transplanted under the renal capsule of immunodeficient mice. One month later, 19 of 28 mice transplanted with ICCs and 4 of 14 mice with IPCs produced human C-peptide detectable in blood, indicating that the in vivo environment further facilitated the maturation of ICCs. However, among the hormone-positive mice, only 9 of 19 mice with ICCs and two of four mice with IPCs were able to secrete C-peptide in response to glucose.
基于分化为功能性胰岛素分泌细胞的能力，干细胞/祖细胞有望缓解/治愈 1 型糖尿病。本研究旨在评估人胰腺 IPC（胰岛衍生祖细胞）的分化潜能。从 4 名供体中分离出 IPC，并在分化为 ICC（胰岛样细胞簇）之前进行了 2000 多倍的扩增。ICC 在 mRNA 水平上表达 ISL-1、Glut2、PDX-1、ngn3、胰岛素、胰高血糖素和生长抑素，并通过免疫荧光法对胰岛素和胰高血糖素呈阳性染色。在体外进行葡萄糖刺激后，在超声 ICC 中检测到 C 肽，而不是在条件培养基中。为了研究细胞在体内的功能，将 IPC 或 ICC 移植到免疫缺陷小鼠的肾包膜下。一个月后，在接受 ICC 移植的 28 只小鼠中有 19 只和接受 IPC 移植的 14 只小鼠中有 4 只在血液中检测到人类 C 肽，表明体内环境进一步促进了 ICC 的成熟。然而，在激素阳性小鼠中，只有 19 只 ICC 移植小鼠中有 9 只和 4 只 IPC 移植小鼠中有 2 只能够对葡萄糖分泌 C 肽。
