Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation
Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation
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DOI：
10.1097/01.tp.0000231708.19937.21
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发表时间：
2006-08-27
期刊：
影响因子：
6.2
通讯作者：
Lowe, William L., Jr.
中科院分区：
文献类型：
--
作者：
Blomeier, Herman;Zhang, Xiaomin;Lowe, William L., Jr.
背景。胰岛肝移植相关的问题可能阻碍胰岛移植的广泛应用。因此，我们试图开发一种使用合成的可生物降解聚合物支架进行胰岛肝外移植的方法。
方法。由丙交酯和乙交酯的共聚物制成允许血管向内生长以及营养物质从宿主组织扩散的微孔聚合物支架。将小鼠胰岛在有或无支架的情况下移植到同基因糖尿病受体的腹腔内脂肪上。使用冷却的电荷耦合器件相机进行生物发光成像、免疫组织化学以及血糖测定来评估移植后胰岛的植入和功能。
结果。通过生物发光成像，移植在聚合物支架上的胰岛仍局限于移植部位并能长时间存活。移植在支架上的胰岛保留了天然胰岛的结构，并形成了功能性胰岛血管系统。与无支架移植相比，在聚合物支架上移植少量胰岛在糖尿病逆转效果方面显示出胰岛功能改善，包括达到正常血糖所需的平均时间、体重增加以及腹腔内葡萄糖耐量试验期间的葡萄糖水平，这表明在聚合物支架上移植少量胰岛时胰岛功能得到改善。
结论。这些发现表明，合成聚合物支架可作为胰岛移植的平台，并且与无支架移植的胰岛相比，可改善肝外移植胰岛的功能。该支架可能还有助于传递生物活性分子以改变移植胰岛周围的微环境，从而提高胰岛的存活率和功能。
Background. Problems associated with the hepatic transplantation of islets may preclude the broad application of islet transplantation. Thus, we sought to develop an approach to the extrahepatic transplantation of islets using a synthetic biodegradable polymer scaffold.Methods. Microporous polymer scaffolds that allow vascular ingrowth and nutrient diffusion from host tissues were fabricated from copolymers of lactide and glycolide. Murine islets were transplanted without or with a scaffold onto intraperitoneal fat of syngeneic diabetic recipients. Bioluminescence imaging using a cooled charge-coupled device camera, immunohistochemistry, and glycemia were used to assess islet engraftment and function posttransplant.Results. By bioluminescence imaging, islets transplanted on a polymer scaffold remain localized to the transplant site and survive for an extended period of time. Islets transplanted on scaffolds retained the architecture of native islets and developed a functional islet vasculature. Transplantation of marginal masses of islets on the polymer scaffold demonstrated improved islet function compared to transplantation without a scaffold as assessed by the effectiveness of diabetes reversal, including mean time required to achieve euglycemia, weight gain, and glucose levels during an intraperitoneal glucose tolerance test.Conclusion. These findings indicate that a synthetic polymer scaffold can serve as a platform for islet transplantation and improves the function of extrahepatically transplanted islets compared to islets transplanted without a scaffold. The scaffold may also be useful to deliver bioactive molecules to modify the microenvironment surrounding the transplanted islets and, thus, enhance islet survival and function.