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诱导多能干细胞衍生的细胞外囊泡促进急性肾损伤模型中的肾保护作用。

Extracellular Vesicles Derived from Induced Pluripotent Stem Cells Promote Renoprotection in Acute Kidney Injury Model.

机构信息

Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.

National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, 21941-902 Rio de Janeiro, Brazil.

出版信息

Cells. 2020 Feb 17;9(2):453. doi: 10.3390/cells9020453.

DOI:10.3390/cells9020453
PMID:32079274
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7072760/
Abstract

Induced pluripotent stem cells (iPSC) have been the focus of several studies due to their wide range of application, including in cellular therapy. The use of iPSC in regenerative medicine is limited by their tumorigenic potential. Extracellular vesicles (EV) derived from stem cells have been shown to support renal recovery after injury. However, no investigation has explored the potential of iPSC-EV in the treatment of kidney diseases. To evaluate this potential, we submitted renal tubule cells to hypoxia-reoxygenation injury, and we analyzed cell death rate and changes in functional mitochondria mass. An in vivo model of ischemia-reperfusion injury was used to evaluate morphological and functional alterations. Gene array profile was applied to investigate the mechanism involved in iPSC-EV effects. In addition, EV derived from adipose mesenchymal cells (ASC-EV) were also used to compare the potential of iPSC-EV in support of tissue recovery. The results showed that iPSC-EV were capable of reducing cell death and inflammatory response with similar efficacy than ASC-EV. Moreover, iPSC-EV protected functional mitochondria and regulated several genes associated with oxidative stress. Taken together, these results show that iPSC can be an alternative source of EV in the treatment of different aspects of kidney disease.

摘要

诱导多能干细胞(iPSC)因其广泛的应用而成为了多项研究的焦点,包括细胞疗法。iPSC 在再生医学中的应用受到其致瘤潜能的限制。已经有研究表明,来源于干细胞的细胞外囊泡(EV)可以支持损伤后的肾脏恢复。然而,目前还没有研究探索 iPSC-EV 在治疗肾脏疾病方面的潜力。为了评估这种潜力,我们将肾小管细胞置于缺氧-复氧损伤中,并分析细胞死亡率和功能线粒体质量的变化。使用缺血再灌注损伤的体内模型来评估形态和功能的改变。基因芯片谱用于研究 iPSC-EV 作用涉及的机制。此外,还使用了来源于脂肪间充质细胞的 EV(ASC-EV)来比较 iPSC-EV 支持组织恢复的潜力。结果表明,iPSC-EV 能够以与 ASC-EV 相似的效果降低细胞死亡和炎症反应。此外,iPSC-EV 还保护了功能线粒体并调节了与氧化应激相关的几个基因。总之,这些结果表明,iPSC 可以作为 EV 的替代来源,用于治疗肾脏疾病的不同方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/38eb789529cb/cells-09-00453-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/581f7ebc8682/cells-09-00453-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/456051a8b33e/cells-09-00453-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/389fcaf2533f/cells-09-00453-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/95d00ab09202/cells-09-00453-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/d8389b05a46b/cells-09-00453-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/38eb789529cb/cells-09-00453-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/581f7ebc8682/cells-09-00453-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/456051a8b33e/cells-09-00453-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/389fcaf2533f/cells-09-00453-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/95d00ab09202/cells-09-00453-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/d8389b05a46b/cells-09-00453-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5774/7072760/38eb789529cb/cells-09-00453-g006.jpg

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