Stem cell-derived extracellular vesicles inhibit and revert fibrosis progression in a mouse model of diabetic nephropathy

被引：192

作者：

Grange, Cristina ^{[1
,2
]}

Tritta, Stefania ^{[2
]}

Tapparo, Marta ^{[1
]}

Cedrino, Massimo ^{[2
]}

Tetta, Ciro ^{[3
]}

Camussi, Giovanni ^{[1
,2
,4
]}

Brizzi, Maria Felice ^{[1
,2
,4
]}

机构：

[1] Univ Turin, Dept Med Sci, Turin, Italy

[2] Univ Turin, Mol Biotechnol Ctr, Turin, Italy

[3] Unicyte Srl, Turin, Italy

[4] Univ Turin, 2I3T Societa Gest Incubatore Imprese & Trasferime, Turin, Italy

来源：

SCIENTIFIC REPORTS | 2019年 / 9卷 / 1期

关键词：

TUBULOINTERSTITIAL FIBROSIS; MESENCHYMAL TRANSITION; MICROVESICLES PROTECT; RENAL INJURY; KIDNEY; EXPRESSION; MICRORNA-146A; REPRESSION; MECHANISM; APOPTOSIS;

D O I：

10.1038/s41598-019-41100-9

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Extracellular vesicles (EVs) that are derived from mesenchymal stromal cells (MSCs) have been shown to reprogram injured cells by activating regenerative processes. We herein investigate the potential therapeutic effect of EVs, shed by human bone marrow MSCs and by human liver stem-like cells (HLSCs), on the progression and reversion of fibrosis in a mouse model of diabetic nephropathy, as induced by streptozotocin. After the development of nephropathy, stem cell-derived EVs were administered weekly to diabetic mice for four weeks. The stem cell-derived EV treatment, but not the fibroblast EV treatment that was used as a control, significantly ameliorated functional parameters, such as albumin/creatinine excretion, plasma creatinine and blood urea nitrogen, which are altered in diabetic mice. Moreover, the renal fibrosis that develops during diabetic nephropathy progression was significantly inhibited in stem cell EV-treated animals. A correlation was found between the down regulation of several pro-fibrotic genes in renal tissues and the anti-fibrotic effect of HLSC and MSC EVs. A comparative analysis of HLSC and MSC EV miRNA content highlighted some common and some specific patterns of miRNAs that target predicted pro-fibrotic genes. In conclusion, stem cell-derived EVs inhibit fibrosis and prevent its progression in a model of diabetes-induced chronic kidney injury.

引用

页数：13

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