Extra-cellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of AKI in a manner comparable to the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSC, it is unclear which population is responsible for the pro-regenerative effects. We therefore evaluated the effect of various EV-populations separated by differential ultracentrifugation (10K population enriched with microvesicles and 100K population enriched with exosomes) on AKI recovery. Only the exosomal-enriched population induced an improvement of renal function and morphology, comparable with that of the total EV population. Interestingly, the 100K EVs exerted a pro-proliferative effect on murine tubular cells, both in vitro and in vivo. Analysis of the molecular content from the different EV populations revealed a distinct profile. The 100K population for instance was enriched in specific mRNAs (CCNB1, CDK8, CDC6) reported to influence cell cycle entry and progression; miRNAs involved in regulating proliferative/anti-apoptotic pathways and growth factors (HGF and IGF-1) that could explain the effect of renal tubular cell proliferation. On the other hand, the EV population enriched in microvesicles (10K), was unable to induce renal regeneration and had a molecular profile with lower expression of pro-proliferative molecules. In conclusion, the different molecular composition of exosome- and microvesicle-enriched populations may explain the regenerative effect of EVs observed in AKI.

Renal regenerative potential of different extra-cellular vesicle populations derived from bone marrow mesenchymal stromal cells

BRUNO, Stefania
First
;
TAPPARO, MARTA;COLLINO, Federica;CHIABOTTO, GIULIA;DEREGIBUS, Maria Chiara;SOARES LINDOSO, RAFAEL;Neri, Francesco;GIUNTI, Sara;CAMUSSI, Giovanni
2017

Abstract

Extra-cellular vesicles (EVs) derived from human bone marrow mesenchymal stromal cells (MSCs) promote the regeneration of kidneys in different animal models of AKI in a manner comparable to the cells of origin. However, due to the heterogeneity observed in the EVs isolated from MSC, it is unclear which population is responsible for the pro-regenerative effects. We therefore evaluated the effect of various EV-populations separated by differential ultracentrifugation (10K population enriched with microvesicles and 100K population enriched with exosomes) on AKI recovery. Only the exosomal-enriched population induced an improvement of renal function and morphology, comparable with that of the total EV population. Interestingly, the 100K EVs exerted a pro-proliferative effect on murine tubular cells, both in vitro and in vivo. Analysis of the molecular content from the different EV populations revealed a distinct profile. The 100K population for instance was enriched in specific mRNAs (CCNB1, CDK8, CDC6) reported to influence cell cycle entry and progression; miRNAs involved in regulating proliferative/anti-apoptotic pathways and growth factors (HGF and IGF-1) that could explain the effect of renal tubular cell proliferation. On the other hand, the EV population enriched in microvesicles (10K), was unable to induce renal regeneration and had a molecular profile with lower expression of pro-proliferative molecules. In conclusion, the different molecular composition of exosome- and microvesicle-enriched populations may explain the regenerative effect of EVs observed in AKI.
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Bruno, Stefania; Tapparo, Marta; Collino, Federica; Chiabotto, Giulia; Deregibus, Maria Chiara; Soares Lindoso, Rafael; Neri, Francesco; Kholia, Sharad; Giunti, Sara; Wen, Sicheng; Quesenberry, Peter; Camussi, Giovanni
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/1645700
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