Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells
Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells
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DOI：
10.1007/s00125-012-2542-0
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发表时间：
2012-07-01
期刊：
影响因子：
8.2
通讯作者：
Heimberg, H.
中科院分区：
文献类型：
--
作者：
Grouwels, G.;Vasylovska, S.;Heimberg, H.
有效刺激培养的β细胞的循环活动将有助于设计糖尿病细胞治疗的新策略。神经嵴干细胞 (NCSC) 在 β 细胞发育和成熟中发挥作用，并增加共移植中的 β 细胞数量。 NCSC 诱导的 β 细胞增殖和新 β 细胞的功能能力背后的机制尚不清楚。我们开发了一种新的体外共培养系统，能够解析控制细胞相互作用的元件，从而导致 NCSC 依赖性胰岛 β 细胞增加。小鼠 NCSC 在体外培养，首先在刺激其增殖的培养基中，然后在支持其分化的条件下培养。当小鼠胰岛细胞与 NCSC 一起培养时，超过 35% 的 β 细胞表现出循环活性。该标记指数比未培养 NCSC 的对照胰岛高十倍以上。在这些培养条件下增殖的β细胞在胰岛素分泌方面具有完全的葡萄糖反应性。 NCSC 还在从 1 岁小鼠分离的胰岛中诱导 β 细胞增殖，但在从人类供体胰腺组织中分离的分离胰岛细胞中则不诱导 β 细胞增殖。为了刺激 β 细胞增殖，NCSC 需要与 β 细胞密切接触。胰岛细胞与 NCSC 接触的培养物可诱导高效的 β 细胞增殖。所报道的培养系统是一个很好的平台，可以进一步剖析驱动这一过程所需的最小因素，并探索其转化为糖尿病治疗的潜力。
Efficient stimulation of cycling activity in cultured beta cells would allow the design of new strategies for cell therapy in diabetes. Neural crest stem cells (NCSCs) play a role in beta cell development and maturation and increase the beta cell number in co-transplants. The mechanism behind NCSC-induced beta cell proliferation and the functional capacity of the new beta cells is not known.We developed a new in vitro co-culture system that enables the dissection of the elements that control the cellular interactions that lead to NCSC-dependent increase in islet beta cells.Mouse NCSCs were cultured in vitro, first in medium that stimulated their proliferation, then under conditions that supported their differentiation. When mouse islet cells were cultured together with the NCSCs, more than 35% of the beta cells showed cycle activity. This labelling index is more than tenfold higher than control islets cultured without NCSCs. Beta cells that proliferated under these culture conditions were fully glucose responsive in terms of insulin secretion. NCSCs also induced beta cell proliferation in islets isolated from 1-year-old mice, but not in dissociated islet cells isolated from human donor pancreas tissue. To stimulate beta cell proliferation, NCSCs need to be in intimate contact with the beta cells.Culture of islet cells in contact with NCSCs induces highly efficient beta cell proliferation. The reported culture system is an excellent platform for further dissection of the minimal set of factors needed to drive this process and explore its potential for translation to diabetes therapy.