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Updated: May 23, 2026
Isolation, Characterization, and Therapeutic Application of Extracellular Vesicles from Cultured Human Mesenchymal Stem Cells
Published on: September 23, 2022
Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury
Stefania Bruno1, Cristina Grange, Federica Collino
1Department of Internal Medicine and Molecular Biotechnology Center, University of Torino, Torino, Italy.
Abstract:
Several studies demonstrated that treatment with mesenchymal stem cells (MSCs) reduces cisplatin mortality in mice. Microvesicles (MVs) released from MSCs were previously shown to favor renal repair in non lethal toxic and ischemic acute renal injury (AKI). In the present study we investigated the effects of MSC-derived MVs in SCID mice survival in lethal cisplatin-induced AKI. Moreover, we evaluated in vitro the effect of MVs on cisplatin-induced apoptosis of human renal tubular epithelial cells and the molecular mechanisms involved. Two different regimens of MV injection were used. The single administration of MVs ameliorated renal function and morphology, and improved survival but did not prevent chronic tubular injury and persistent increase in BUN and creatinine. Multiple injections of MVs further decreased mortality and at day 21 surviving mice showed normal histology and renal function. The mechanism of protection was mainly ascribed to an anti-apoptotic effect of MVs. In vitro studies demonstrated that MVs up-regulated in cisplatin-treated human tubular epithelial cells anti-apoptotic genes, such as Bcl-xL, Bcl2 and BIRC8 and down-regulated genes that have a central role in the execution-phase of cell apoptosis such as Casp1, Casp8 and LTA. In conclusion, MVs released from MSCs were found to exert a pro-survival effect on renal cells in vitro and in vivo, suggesting that MVs may contribute to renal protection conferred by MSCs.
Insights
Mesenchymal stem cell-derived microvesicles (MVs) protect against lethal cisplatin-induced acute kidney injury (AKI) in mice. Multiple MV injections improved survival and restored renal function by reducing apoptosis in kidney cells.
Area of Science:
- Nephrology
- Regenerative Medicine
- Cell Biology
Background:
- Mesenchymal stem cells (MSCs) reduce mortality in cisplatin-induced acute kidney injury (AKI).
- MSCs-derived microvesicles (MVs) promote renal repair in non-lethal AKI.
- The protective effects of MSC-MVs in lethal AKI remain to be fully elucidated.
Purpose of the Study:
- To investigate the efficacy of MSC-derived MVs in improving survival in a lethal cisplatin-induced AKI mouse model.
- To evaluate the in vitro effects of MVs on cisplatin-induced apoptosis in human renal tubular epithelial cells.
- To explore the molecular mechanisms underlying MV-mediated renal protection.
Main Methods:
- SCID mice were subjected to lethal cisplatin-induced AKI and treated with single or multiple injections of MSC-derived MVs.
- Renal function, histology, and survival rates were assessed.
- In vitro studies involved treating human renal tubular epithelial cells with cisplatin and MVs to analyze apoptosis and gene expression.
Main Results:
- Single MV administration improved renal function and survival but did not prevent chronic injury.
- Multiple MV injections significantly decreased mortality, leading to normal histology and renal function by day 21.
- In vitro, MVs reduced cisplatin-induced apoptosis by up-regulating anti-apoptotic genes (Bcl-xL, Bcl2, BIRC8) and down-regulating pro-apoptotic genes (Casp1, Casp8, LTA).
Conclusions:
- MSC-derived MVs exert a pro-survival effect on renal cells in both in vitro and in vivo settings.
- Multiple MV administrations are crucial for complete recovery from lethal cisplatin-induced AKI.
- MVs represent a promising cell-free therapeutic strategy for AKI, potentially mediating renal protection through anti-apoptotic mechanisms.
