Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.
Transplantation. 2010 Dec 27;90(12):1366-73. doi: 10.1097/TP.0b013e3181ffba31.
Overcoming significant loss of transplanted islet mass is important for successful islet transplantation. Adipose tissue-derived stem cells (ADSCs) seem to have angiogenic potential and antiinflammatory properties. We hypothesized that the inclusion of ADSCs with islet transplantation should enhance the survival and insulin function of the islet graft.
Syngeneic ADSCs and allogeneic islets were transplanted simultaneously under the kidney capsules of diabetic C57BL/6J mice. Rejection of the graft was examined by measurement of blood glucose level. Revascularization and inflammatory cell infiltration were examined by immunohistochemistry.
Transplantation of 400 islets only achieved normoglycemia with graft survival of 13.6±1.67 days (mean±standard deviation), whereas that of 100 or 200 allogeneic islets never reversed diabetes. Transplantation of 200 islets with 2×10(5) ADSCs reversed diabetes and significantly prolonged graft survival (13.0±5.48 days). Results of glucose tolerance tests performed on day 7 were significantly better in islets-ADSCs than islets-alone recipients. Immunohistochemical analysis confirmed the presence of insulin-stained islet grafts with well-preserved structure in islets-ADSCs transplant group. Significant revascularization (larger number of von Willebrand factor-positive cells) and marked inhibition of inflammatory cell infiltration, including CD4+ and CD8+ T cells and macrophages, were noted in the islets-ADSCs transplant group than islets-alone transplant group.
Our results indicated that cotransplantation of ADSCs with islet graft promoted survival and insulin function of the graft and reduced the islet mass required for reversal of diabetes. This innovative protocol may allow "one donor to one recipient" islet transplantation.
克服移植胰岛质量的大量损失对于成功的胰岛移植非常重要。脂肪组织来源的干细胞（ADSCs）似乎具有血管生成潜力和抗炎特性。我们假设，将 ADSC 与胰岛移植结合使用应能增强胰岛移植物的存活和胰岛素功能。
将同基因 ADSC 和同种异体胰岛同时移植到糖尿病 C57BL/6J 小鼠的肾包膜下。通过测量血糖水平来检查移植物的排斥反应。通过免疫组织化学检查血管再生和炎症细胞浸润。
仅移植 400 个胰岛仅能使血糖正常化，移植物的存活率为 13.6±1.67 天（平均值±标准差），而 100 或 200 个同种异体胰岛从未逆转糖尿病。移植 200 个胰岛并联合 2×10(5)个 ADSC 逆转了糖尿病，并显著延长了移植物的存活时间（13.0±5.48 天）。第 7 天进行的葡萄糖耐量试验结果表明，胰岛-ADSC 组明显优于胰岛单独组。免疫组织化学分析证实，在胰岛-ADSC 移植组中，胰岛移植物存在胰岛素染色的胰岛，其结构保存完好。在胰岛-ADSC 移植组中观察到明显的血管再生（更多的血管性血友病因子阳性细胞）和炎症细胞浸润（包括 CD4+和 CD8+T 细胞和巨噬细胞）的显著抑制，明显优于胰岛单独移植组。
我们的结果表明，ADSC 与胰岛移植物共移植可促进移植物的存活和胰岛素功能，并减少逆转糖尿病所需的胰岛质量。这种创新方案可能允许“一个供体一个受体”的胰岛移植。
