Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes.

Co-Microencapsulation of Islets and MSC CellSaics, Mosaic-Like Aggregates of MSCs and Recombinant Peptide Pieces, and Therapeutic Effects of Their Subcutaneous Transplantation on Diabetes.
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DOI:
10.3390/biomedicines8090318
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发表时间:
2020-08-31
期刊:
影响因子:
4.7
通讯作者:
Yoshioka Y
Yoshioka Y
中科院分区:
工程技术3区
文献类型:
--
作者:
Mochizuki Y;Kogawa R;Takegami R;Nakamura K;Wakabayashi A;Ito T;Yoshioka Y

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微囊化胰岛的皮下移植作为I型糖尿病的治疗方法已被广泛研究。然而,由于皮下区域较低的血管密度和强烈的炎症反应,很少有成功恢复血糖水平的报道。为了解决这个问题,我们开发了由间充质干细胞(MSC)和称为MSC CellSaics的重组肽片段组成的马赛克样聚集体,其提供了血管生成因子和抗炎细胞因子的连续释放。我们以前的报告显示,MSC CellSaics和大鼠胰岛皮下共移植可逆转免疫缺陷型糖尿病模型小鼠的糖尿病。在这项研究中,我们专注于免疫隔离微囊的开发,以共同封装MSC CellSaics和大鼠胰岛,以及通过皮下移植到免疫活性糖尿病模型小鼠的治疗效果。当在移植后28天监测血糖水平时,证实新免疫隔离微囊的正常化率显著高于不含MSC CellSaics的微囊和移植到微囊外部的MSC CellSaics的正常化率(p < 0.01)。此外,治疗所需的胰岛数量减少。在染色的切片中,在新的免疫隔离微胶囊周围观察到更大数量/面积的血管,这表明MSC CellSaics通过微胶囊分泌的血管生成因子局部发挥作用以增强其功效。
The subcutaneous transplantation of microencapsulated islets has been extensively studied as a therapeutic approach for type I diabetes. However, due to the lower vascular density and strong inflammatory response in the subcutaneous area, there have been few reports of successfully normalized blood glucose levels. To address this issue, we developed mosaic-like aggregates comprised of mesenchymal stem cells (MSCs) and recombinant peptide pieces called MSC CellSaics, which provide a continuous release of angiogenic factors and anti-inflammatory cytokines. Our previous report revealed that the diabetes of immunodeficient diabetic model mice was reversed by the subcutaneous co-transplantation of the MSC CellSaics and rat islets. In this study, we focused on the development of immune-isolating microcapsules to co-encapsulate the MSC CellSaics and rat islets, and their therapeutic efficiency via subcutaneous transplantation into immunocompetent diabetic model mice. As blood glucose level was monitored for 28 days following transplantation, the normalization rate of the new immuno-isolating microcapsules was confirmed to be significantly higher than those of the microcapsules without the MSC CellSaics, and the MSC CellSaics transplanted outside the microcapsules (p < 0.01). Furthermore, the number of islets required for the treatment was reduced. In the stained sections, a larger number/area of blood vessels was observed around the new immuno-isolating microcapsules, which suggests that angiogenic factors secreted by the MSC CellSaics through the microcapsules function locally for their enhanced efficacy.
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