Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
BIOMATCELL, VINN Excellence Center of Biomaterials and Cell Therapy, Gothenburg, Sweden.
PLoS One. 2018 Feb 15;13(2):e0193059. doi: 10.1371/journal.pone.0193059. eCollection 2018.
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.
人骨髓间充质干细胞（hMSC）来源的外泌体具有再生作用，但它们在成骨中的作用及其潜在机制尚待确定。在本研究中，我们研究了 hMSC 在整个成骨分化过程中外泌体的时间进程分泌。来自不同成骨分化阶段的 hMSC 的外泌体使同源细胞向成骨谱系分化，但只有来自成骨分化晚期的外泌体诱导细胞外基质矿化。来自扩增和早期及晚期成骨分化的外泌体被 hMSC 的一个亚群内化。miRNA 谱分析显示了一组来自成骨分化晚期的差异表达外泌体 miRNA，这些 miRNA 与成骨相关。靶预测表明，这些 miRNA 富集了与调节成骨分化和外泌体发挥作用的一般机制相关的途径，如“Wnt 信号通路”和“内吞作用”。总之，这些结果表明，MSCs 根据其亲本细胞的分化阶段分泌具有不同生物学特性的外泌体。来自分化晚期的 MSC 的外泌体转移物诱导成骨分化和矿化。此外，提示外泌体对成骨的调节作用至少部分是通过外泌体 miRNA 发挥的。
