Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats.

Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats.
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三维聚集体增强脂肪间充质干细胞对大鼠缺血再灌注肾损伤的治疗作用

DOI:
10.1155/2016/9062638
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发表时间:
2016
影响因子:
4.3
通讯作者:
Guo H
Guo H
中科院分区:
医学3区
文献类型:
--
作者:
Zhao X;Qiu X;Zhang Y;Zhang S;Gu X;Guo H

文献摘要

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脂肪间充质干细胞(AdMSCs)的应用促进了肾缺血再灌注损伤的结构和功能恢复。然而,干细胞的低植入限制了AdMSCs的治疗效果。本研究旨在通过以三维(3D)聚集体形式递送AdMSCs来增强AdMSCs的治疗效果。微孔用于产生3D AdMSC聚集体。体外实验结果表明,与二维单层培养的AdMSCs相比,三维聚集体中的AdMSCs对200 μM过氧化氢和缺氧/复氧诱导的氧化应激和缺氧应激的敏感性降低。此外,在三维聚集体中的AdMSCs比在二维单层中培养的AdMSCs分泌更多的促血管生成因子。在诱导肾IR损伤后立即将2D AdMSCs或3D AdMSCs聚集体注射到肾皮质。在体内数据显示,3D聚集体增强了AdMSCs在肾IR损伤后恢复功能和结构的作用。与在2D单层中培养的AdMSCs相比,在注射有3D聚集体的肾脏中观察到改进的移植AdMSCs。我们的研究结果表明,三维AdMSCs聚集的微孔产生的增强了AdMSCs的保留和对肾IR损伤的治疗作用。
It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia-reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three-dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.