Combined Transplantation of Pancreatic Islets and Adipose Tissue-Derived Stem Cells Enhances the Survival and Insulin Function of Islet Grafts in Diabetic Mice
Combined Transplantation of Pancreatic Islets and Adipose Tissue-Derived Stem Cells Enhances the Survival and Insulin Function of Islet Grafts in Diabetic Mice
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DOI：
10.1097/tp.0b013e3181ffba31
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发表时间：
2010-12-27
期刊：
影响因子：
6.2
通讯作者：
Mori, Masaki
中科院分区：
文献类型：
--
作者：
Ohmura, Yoshiaki;Tanemura, Masahiro;Mori, Masaki
背景克服移植胰岛质量的显著损失对于成功的胰岛移植是重要的。脂肪组织来源的干细胞（ADSCs）似乎具有血管生成潜能和增殖特性。我们推测，胰岛移植中加入脂肪干细胞可以提高胰岛移植物的存活率和胰岛素功能。将同基因脂肪干细胞和同种异体胰岛同时移植到糖尿病C57 BL/6 J小鼠的肾被膜下。通过测量血糖水平来检查移植物的排斥反应。免疫组化检测血运重建和炎性细胞浸润。移植400个胰岛仅达到正常血糖，移植物存活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。200个胰岛与2 × 105个ADSC的移植逆转了糖尿病，并显著延长了移植物存活期（13.0 +/- 5.48天）。在第7天进行的葡萄糖耐量试验的结果在胰岛-ADSC中比单独的胰岛受体明显更好。免疫组化分析证实胰岛-ADSCs移植组中存在胰岛素染色的胰岛移植物，其结构保存良好。与单纯胰岛移植组相比，胰岛-ADSCs移植组血管再生明显（血管性血友病因子阳性细胞数量增多），炎性细胞浸润（包括CD 4+、CD 8 + T细胞和巨噬细胞）明显受到抑制。我们的研究结果表明，ADSCs与胰岛移植物共移植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。这种创新的方案可能允许“一个供体对一个受体”的胰岛移植。
Background. 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.Methods. 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.Results. 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 x 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.Conclusions. 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.