Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization.
Endothelial progenitor cell cotransplantation enhances islet engraftment by rapid revascularization.
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作者：
Kang S;Park HS;Jo A;Hong SH;Lee HN;Lee YY;Park JS;Jung HS;Chung SS;Park KS
移植胰岛的血运重建受损是导致进行性胰岛丧失的关键问题。由于已知内皮祖细胞 (EPC) 有助于新血管形成，因此我们旨在通过将 EPC 与胰岛共移植来增强胰岛移植。将带有（胰岛 EPC 组）或不带有（仅胰岛组）人脐带血来源的 EPC 的猪胰岛移植到糖尿病裸鼠中。胰岛 EPC 组在移植后约 11 天达到正常血糖，而仅胰岛组则没有。此外，胰岛-EPC 组的血清猪胰岛素水平高于仅胰岛组。来自胰岛-EPC 组的胰岛在移植早期更快速地血运重建，而完全血运重建的移植物的最终毛细血管密度没有增加。胰岛-EPC 组血运重建率的提高主要归因于刺激移植物产生血管内皮生长因子-A。 EPC 联合移植的快速血运重建导致更好的移植物灌注和缺氧恢复。 EPC 共移植还与更大的 β 细胞增殖相关，可能是由于更多的基底膜产生和肝细胞生长因子分泌。总之，EPCs和胰岛的联合移植通过提高移植物血运重建率来诱导更好的胰岛植入。这些发现可能为提高临床实践中胰岛移植的疗效提供直接适用的工具。
Impaired revascularization of transplanted islets is a critical problem that leads to progressive islet loss. Since endothelial progenitor cells (EPCs) are known to aid neovascularization, we aimed to enhance islet engraftment by cotransplanting EPCs with islets. Porcine islets, with (islet-EPC group) or without (islet-only group) human cord blood–derived EPCs, were transplanted into diabetic nude mice. The islet-EPC group reached euglycemia by ∼11 days posttransplantation, whereas the islet-only group did not. Also, the islet-EPC group had a higher serum porcine insulin level than the islet-only group. Islets from the islet-EPC group were more rapidly revascularized at the early period of transplantation without increment of final capillary density at the fully revascularized graft. Enhanced revascularization rate in the islet-EPC group was mainly attributed to stimulating vascular endothelial growth factor-A production from the graft. The rapid revascularization by EPC cotransplantation led to better graft perfusion and recovery from hypoxia. EPC cotransplantation was also associated with greater β-cell proliferation, probably by more basement membrane production and hepatocyte growth factor secretion. In conclusion, cotransplantation of EPCs and islets induces better islet engraftment by enhancing the rate of graft revascularization. These findings might provide a directly applicable tool to enhance the efficacy of islet transplantation in clinical practice.
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