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通过植入经磁纯化的微囊化假胰岛实现 1 型糖尿病逆转。

Type 1 Diabetes Mellitus reversal via implantation of magnetically purified microencapsulated pseudoislets.

机构信息

NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country (UPV/EHU), Paseo de la Universidad 7, 01006 Vitoria-Gasteiz, Spain; Biomedical Research Networking Center in Bioengineering, Biomaterials, and Nanomedicine (CIBER-BBN), Vitoria-Gasteiz, Spain.

BIOMICs-microfluidics Research Group, Microfluidics Cluster UPV/EHU, University of the Basque Country, Spain.

出版信息

Int J Pharm. 2019 Apr 5;560:65-77. doi: 10.1016/j.ijpharm.2019.01.058. Epub 2019 Feb 10.

Abstract

Microencapsulation of pancreatic islets for the treatment of Type I Diabetes Mellitus (T1DM) generates a high quantity of empty microcapsules, resulting in high therapeutic graft volumes that can enhance the host's immune response. We report a 3D printed microfluidic magnetic sorting device for microcapsules purification with the objective to reduce the number of empty microcapsules prior transplantation. In this study, INS1E pseudoislets were microencapsulated within alginate (A) and alginate-poly-L-lysine-alginate (APA) microcapsules and purified through the microfluidic device. APA microcapsules demonstrated higher mechanical integrity and stability than A microcapsules, showing better pseudoislets viability and biological function. Importantly, we obtained a reduction of the graft volume of 77.5% for A microcapsules and 78.6% for APA microcapsules. After subcutaneous implantation of induced diabetic Wistar rats with magnetically purified APA microencapsulated pseudoislets, blood glucose levels were restored into normoglycemia (<200 mg/dL) for almost 17 weeks. In conclusion, our described microfluidic magnetic sorting device represents a great alternative approach for the graft volume reduction of microencapsulated pseudoislets and its application in T1DM disease.

摘要

3D 打印微流控磁分选装置用于微胶囊的纯化,以减少移植前的空微胶囊数量。在这项研究中,INS1E 假胰岛细胞被包裹在藻酸盐(A)和藻酸盐-聚-L-赖氨酸-藻酸盐(APA)微胶囊内,并通过微流控装置进行纯化。APA 微胶囊表现出更高的机械完整性和稳定性,比 A 微胶囊具有更好的假胰岛细胞活力和生物学功能。重要的是,我们获得了 A 微胶囊和 APA 微胶囊的移植物体积减少 77.5%和 78.6%。将经磁纯化的 APA 微囊化假胰岛细胞皮下植入诱导糖尿病 Wistar 大鼠后,血糖水平恢复正常(<200mg/dL)近 17 周。总之,我们描述的微流控磁分选装置为减少微囊化假胰岛细胞的移植物体积提供了一种很好的替代方法,并可应用于 1 型糖尿病。

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