Eshpeter A, Jiang J, Au M, Rajotte R V, Lu K, Lebkowski J S, Majumdar A S, Korbutt G S
Alberta Diabetes Institute andDepartment of Surgery, University of Alberta, Edmonton, Canada, andGeron Corporation, Menlo Park, CA, USA.
Cell Prolif. 2008 Dec;41(6):843-858. doi: 10.1111/j.1365-2184.2008.00564.x.
Islet-like clusters (ILCs), differentiated from human embryonic stem cells (hESCs), were characterized both before and after transplantation under the kidney capsule of streptozotocin-induced diabetic immuno-incompetent mice.
Multiple independent ILC preparations (n = 8) were characterized by immunohistochemistry, flow cytometry and cell insulin content, with six preparations transplanted into diabetic mice (n = 42), compared to controls, which were transplanted with either a human fibroblast cell line or undifferentiated hESCs (n = 28).
Prior to transplantation, ILCs were immunoreactive for the islet hormones insulin, C-peptide and glucagon, and for the ductal epithelial marker cytokeratin-19. ILCs also had cellular insulin contents similar to or higher than human foetal islets. Expression of islet and pancreas-specific cell markers was maintained for 70 days post-transplantation. The mean survival of recipients was increased by transplanted ILCs as compared to transplanted human fibroblast cells (P < 0.0001), or undifferentiated hESCs (P < 0.042). Graft function was confirmed by secretion of human C-peptide in response to an oral bolus of glucose.
hESC-derived ILC grafts continued to contain cells that were positive for islet endocrine hormones and were shown to be functional by their ability to secrete human C-peptide. Further enrichment and maturation of ILCs could lead to generation of a sufficient source of insulin-producing cells for transplantation into patients with type 1 diabetes.
对从人胚胎干细胞（hESC）分化而来的胰岛样细胞簇（ILC）在链脲佐菌素诱导的免疫功能不全糖尿病小鼠肾被膜下移植前后进行特征分析。
通过免疫组织化学、流式细胞术和细胞胰岛素含量对多个独立的ILC制剂（n = 8）进行特征分析，将六种制剂移植到糖尿病小鼠体内（n = 42），并与移植了人成纤维细胞系或未分化hESC的对照组（n = 28）进行比较。
移植前，ILC对胰岛激素胰岛素、C肽和胰高血糖素以及导管上皮标志物细胞角蛋白-19具有免疫反应性。ILC的细胞胰岛素含量也与人类胎儿胰岛相似或更高。移植后70天，胰岛和胰腺特异性细胞标志物的表达得以维持。与移植人成纤维细胞（P < 0.0001）或未分化hESC（P < 0.042）相比，移植ILC可提高受体的平均存活时间。口服葡萄糖推注后，人C肽的分泌证实了移植物的功能。
hESC来源的ILC移植物持续含有对胰岛内分泌激素呈阳性的细胞，并通过其分泌人C肽的能力显示出功能。ILC的进一步富集和成熟可能会产生足够的胰岛素产生细胞来源，用于移植到1型糖尿病患者体内。
