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首页> 外文期刊>Cell transplantation >Reversal of diabetes in mice with a bioengineered islet implant incorporating a type I collagen hydrogel and sustained release of vascular endothelial growth factor
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Reversal of diabetes in mice with a bioengineered islet implant incorporating a type I collagen hydrogel and sustained release of vascular endothelial growth factor

机译：生物工程化的胰岛植入物结合了I型胶原水凝胶并持续释放血管内皮生长因子，从而逆转了小鼠的糖尿病

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We have developed a bioengineered implant (BI) to evaluate strategies to promote graft survival and function in models of islet transplantation in mice. The BI, sized for implantation within a fold of intestinal mesentery, consists of a disk-shaped, polyvinyl alcohol sponge infused with a type I collagen hydrogel that contains dispersed donor islets. To promote islet vascularization, the BI incorporates a spherical alginate hydrogel for sustained release of vascular endothelial growth factor (VEGF). BIs that contained 450-500 islets from syngeneic (C57Bl/6) donors and 20 ng of VEGF reversed streptozotocin (STZ)-induced diabetes in 100% of mice (8/8), whereas BIs that contained an equivalent number of islets, but which lacked VEGF, reversed STZ-induced diabetes in only 62.5% of mice (5/8). Between these "+VEGF" and "-VEGF" groups, the time to achieve normoglycemia (8-18 days after implantation) did not differ statistically; however, transitory, postoperative hypoglycemia was markedly reduced in the +VEGF group relative to the -VEGF group. Notably, none of the mice that achieved normoglycemia in these two groups required exogenous insulin therapy once the BIs began to fully regulate levels of blood glucose. Moreover, the transplanted mice responded to glucose challenge in a near-normal manner, as compared to the responses of healthy, nondiabetic (control) mice that had not received STZ. In future studies, the BIs described here will serve as platforms to evaluate the capability of immunomodulatory compounds, delivered locally within the BI, to prevent or reverse diabetes in the setting of autoimmune (type 1) diabetes.
机译：我们已经开发了一种生物工程植入物（BI），以评估在小鼠胰岛移植模型中促进移植物存活和功能的策略。 BI的大小适合植入肠系膜的折叠中，由盘形聚乙烯醇海绵注入，该海绵中注入了I型胶原水凝胶，其中包含分散的供体胰岛。为了促进胰岛血管形成，BI掺入了球形藻酸盐水凝胶，用于持续释放血管内皮生长因子（VEGF）。在100％的小鼠（8/8）中，BIs包含来自同系（C57Bl / 6）供体的450-500个胰岛和20 ng VEGF逆转链脲佐菌素（STZ）诱导的糖尿病，而BIs包含同等数量的胰岛，但是缺乏VEGF的小鼠，只有62.5％（5/8）的小鼠逆转了STZ诱导的糖尿病。在这些“ + VEGF”和“ -VEGF”组之间，达到正常血糖水平的时间（植入后8-18天）在统计学上没有差异;然而，相对于-VEGF组，+ VEGF组的术后短暂性低血糖明显降低。值得注意的是，一旦BI开始完全调节血糖水平，在这两组中均达到正常血糖水平的小鼠均不需要外源胰岛素治疗。此外，与未接受STZ的健康，非糖尿病（对照）小鼠的反应相比，移植小鼠对葡萄糖激发的反应接近于正常方式。在未来的研究中，这里描述的BI将作为平台来评估BI内局部递送的免疫调节化合物预防或逆转自身免疫性（1型）糖尿病的糖尿病的能力。

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