Am J Transl Res. 2016 Oct 15;8(10):4289-4299. eCollection 2016.

Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats.

Zou X¹, Gu D², Xing X³, Cheng Z⁴, Gong D², Zhang G⁵, Zhu Y⁶.

Abstract

BACKGROUND:

Mesenchymal stromal cells (MSCs) derived extracellular vesicles (EVs) were regarded as a potent medium for kidney injury repair and angiogenesis were regarded as an important step in tissue regeneration. However, the pro-angiogenesis effect of MSC-EVs in ischemia-reperfusion induced kidney injury and its potential mechanisms have yet to be determined.

METHODS:

EVs were isolated from the medium of human umbilical cord-derived MSCs (huMSCs) were injected in rats intravenously after unilateral kidney ischemia. Animals were sacrificed at 24 h and 2 weeks after injury. The renal functions and histology staining were examined to assess the therapeutic effect of the EVs. Moreover, we investigated the pro-angiogenesis effects of EVs in injured kidneys and tested the angiogenesis-related factors to further illuminate the probable mechanisms.

RESULTS:

It was observed that EVs could reduce cell apoptosis and enhances proliferation 24 h after kidney injury, meanwhile renal function was improved and the histological lesion was mitigated. Moreover, renal VEGF was up-regulated by EVs and HIF-1α was down-regulated. Further, the increase of capillary vessel density and reduce of renal fibrosis was observed after 2 weeks. In vitro, EVs could deliver human VEGF directly to renal tubular epithelial cells (TECs) and increase VEGF levels. Most important, all the beneficial effects of EVs were abrogated by RNase treated except for the delivery of human VEGF.

CONCLUSIONS:

Human MSC-EVs could protect against ischemic/reperfusion injury induced kidney injury through pro-angiogenesis effects in HIF-1α independent manner, and both the delivery of pro-angiogenesis related VEGF and RNAs were involved in this process.