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Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation

Journal article
Authors Xiaoqin Wang
Omar Omar
Forugh Vazirisani
Peter Thomsen
Karin Ekström
Published in PLoS ONE
Volume 13
Issue 2
Pages e0193059
ISSN 1932-6203
Publication year 2018
Published at Institute of Clinical Sciences, Department of Biomaterials
Pages e0193059
Language en
Links dx.doi.org/10.1371/journal.pone.019...
Keywords human bone-marrow, extracellular vesicles, mediated transfer, stromal, cells, neural cells, expression, mir-31, angiogenesis, regeneration, osteoporosis
Subject categories Biomaterials Science

Abstract

Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as "Wnt signalling pathway" and "endocytosis". Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA.

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