A novel approach to increase human islet cell mass while preserving β-cell function
A novel approach to increase human islet cell mass while preserving β-cell function
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DOI：
10.2337/diabetes.51.12.3435
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发表时间：
2002-12-01
期刊：
影响因子：
7.7
通讯作者：
Hayek, A
中科院分区：
文献类型：
--
作者：
Beattie, GM;Montgomery, AMP;Hayek, A
单层培养中的人类胰岛扩展会导致功能和衰老的丧失。通过维持纤维蛋白凝胶中胰岛的3-D构型，可以响应于肝细胞生长因子（HGF）扩展β细胞，同时在移植到裸小鼠中后体外和体内保留生理葡萄糖的反应。胰岛是有或没有生长因子和烟酰胺的培养自由浮动的，以及具有相同条件的纤维蛋白凝胶。仅在纤维蛋白凝胶和鸡尾酒中培养的胰岛中观察到增殖。总胰岛素增加了三倍，形态计量法的P细胞质量伴随增加。还保留了葡萄糖挑战后的胰岛素释放。纤维蛋白凝胶中的胰岛产生了富含胰岛素和胰高血糖素的大型移植物的体内，并且自由浮动小岛的移植物较小，内分泌细胞较少。循环的人类C肽水平高于接受自由浮动胰岛的小鼠。总而言之，纤维蛋白允许HGF介导的细胞增殖，同时在保留细胞细胞接触的环境中保留葡萄糖反应性。在这些条件下，有限的胰岛离体扩张可能会提高受体 - 唐纳组织比率，以等于全器官移植的功能结果。
Human islet expansion in monolayer culture leads to loss of function and senescence. By maintaining the 3-D configuration of islets in fibrin gels, it is feasible to expand beta-cells in response to hepatocyte growth factor (HGF) while preserving physiologic glucose responsiveness both in vitro and in vivo after transplantation into nude mice. Islets were cultured free floating with or without growth factors and nicotinamide and in fibrin gels with the same conditions. Proliferation was observed only in islets cultured in fibrin gels and the cocktail; total insulin increased by threefold, with a concomitant increase in P-cell mass by morphometry. Insulin release after glucose challenge was also preserved. Islets in fibrin gels gave rise in vivo to large grafts rich in insulin and glucagon, and grafts from free-floating islets were smaller with fewer endocrine cells. Circulating human C-peptide levels were higher than in the mice receiving free-floating islets. In summary, fibrin allows for HGF-mediated cell proliferation while preserving glucose responsiveness in an environment that preserves cell-cell contacts. Limited islet ex vivo expansion under these conditions may improve recipient-donor tissue ratios to equal the functional results of whole-organ transplants.