Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
Electrofusion of mesenchymal stem cells and islet cells for diabetes therapy: a rat model.
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用于糖尿病治疗的间充质干细胞和胰岛细胞的电融合：大鼠模型。
DOI：
10.1371/journal.pone.0064499
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sumi S
中科院分区：
文献类型：
--
作者：
Yanai G;Hayashi T;Zhi Q;Yang KC;Shirouzu Y;Shimabukuro T;Hiura A;Inoue K;Sumi S
胰岛移植是治疗重症糖尿病的一种微创治疗方法。然而，它往往需要多个供体才能实现胰岛素独立，长期效果尚不令人满意。因此，人们探索了克服这些问题的新方法。孤立的胰岛很脆弱，容易受到促凋亡因子的影响，增殖能力很差。相比之下，间充质干细胞(MSCs)具有高度的增殖性、抗凋亡性和多能性，可以分化为多种细胞类型，促进血管生成和调节炎症，因此被认为是胰岛功能和植入的增强剂。电融合是一种有效的细胞融合方法，核重编程发生在不同细胞类型之间的杂交细胞中。因此，我们假设MSC和胰岛细胞之间的电融合可能产生用于糖尿病治疗的强大的胰岛细胞。我们建立了一种分散的胰岛细胞与骨髓间充质干细胞电融合的方法。融合细胞在体外可维持20天的葡萄糖反应性胰岛素释放。从次优胰岛(1000个胰岛)制备的融合细胞肾被膜下移植，即使与MSCs共移植也不能纠正高血糖，在观察期内，在链脲佐菌素诱导的糖尿病大鼠中，融合细胞引起缓慢但持续的血糖下降和显著的体重增加。在大鼠胰岛细胞与小鼠骨髓间充质干细胞的融合细胞中，RT-PCR显示大鼠骨髓间充质干细胞相关基因和小鼠β细胞相关基因都有新的表达，这表明β细胞和骨髓间充质干细胞的核都是双向重编程的。此外，caspase3在胰岛细胞核中的表达减少，Ki-67在胰岛细胞核中的表达增加，分别提示细胞的凋亡和增殖能力的增强。这些结果表明，骨髓间充质干细胞与胰岛细胞电融合产生具有β细胞功能的特殊细胞，并且具有骨髓间充质干细胞的健壮性，有望成为糖尿病治疗的新策略。
Islet transplantation is a minimally invasive treatment for severe diabetes. However, it often requires multiple donors to accomplish insulin-independence and the long-term results are not yet satisfying. Therefore, novel ways to overcome these problems have been explored. Isolated islets are fragile and susceptible to pro-apoptotic factors and poorly proliferative. In contrast, mesenchymal stem cells (MSCs) are highly proliferative, anti-apoptotic and pluripotent to differentiate toward various cell types, promote angiogenesis and modulate inflammation, thereby studied as an enhancer of islet function and engraftment. Electrofusion is an efficient method of cell fusion and nuclear reprogramming occurs in hybrid cells between different cell types. Therefore, we hypothesized that electrofusion between MSC and islet cells may yield robust islet cells for diabetes therapy. We establish a method of electrofusion between dispersed islet cells and MSCs in rats. The fusion cells maintained glucose-responsive insulin release for 20 days in vitro. Renal subcapsular transplantation of fusion cells prepared from suboptimal islet mass (1,000 islets) that did not correct hyperglycemia even if co-transplanted with MSCs, caused slow but consistent lowering of blood glucose with significant weight gain within the observation period in streptozotocin-induced diabetic rats. In the fusion cells between rat islet cells and mouse MSCs, RT-PCR showed new expression of both rat MSC-related genes and mouse β-cell-related genes, indicating bidirectional reprogramming of both β-cell and MSCs nuclei. Moreover, decreased caspase3 expression and new expression of Ki-67 in the islet cell nuclei suggested alleviated apoptosis and gain of proliferative capability, respectively. These results show that electrofusion between MSCs and islet cells yield special cells with β-cell function and robustness of MSCs and seems feasible for novel therapeutic strategy for diabetes mellitus.
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DOI：
10.1159/000092971
发表时间：
2006-01-01
期刊：
INFECTION AND INFLAMMATION : IMPACTS ON ONCOGENESIS
影响因子：
--
作者：
Dittmar, Thomas;Seidel, Jeanette;Niggemann, Bernd
通讯作者：
Niggemann, Bernd
影响因子：
6.5
作者：
Erices, A;Conget, P;Minguell, JJ
通讯作者：
Minguell, JJ
影响因子：
4
作者：
Bell, Gillian I.;Broughton, Heather C.;Hess, David A.
通讯作者：
Hess, David A.
影响因子：
5.2
作者：
in't Anker, PS;Scherjon, SA;Kanhai, HHH
通讯作者：
Kanhai, HHH
影响因子：
7.5
作者：
Barrera-Escorcia, E;Muñóz-Torres, A;Román-Ramos, R
通讯作者：
Román-Ramos, R