作者：Yufei; Ma; Wenting; Yu; Feng; Xumodulationeffectsthe3dstrainmicroenvironmentcharacteristicsmesenchymalstemexosomes
摘要：It is necessary to investigate the characteristics of Mesenchymal stem cells(MSCs)derived exosomes,and especially their application in tissue regeneration.Previous studies have shown that inflammatory stimulation enhanced the secretion of MSC-derived exosomes with stronger anti-inflammatory protein,cytokine profiles,and functional RNA via altering COX2/PGE2 pathway.Recently,accumulating evidence has also revealed that biophysical cues(especially biomechanical cues)in cell microenvironment have significant effects not only on cells but also on their exosomes.It has been reported that applying bi-axial strain to MSCs induces formation of a stiffer cytoskeleton through mTORC2 signaling,which biases against adipogenic differentiation and toward osteoblastogenesis.At the same time,For example,dimensionality,composition and stiffness of the extracellular matrix(ECM)has been proved to affect the size and composition of exosomes secreted by cancer cells.However,the effects of biomechanical cues in the three-dimensional(3D)microenvironment on stem cell-derived exosomes remains to be unveiled.Therefore,it is important to understand the roles of 3D cell mechanical microenvironment in regulating the characteristics of stem cell-derived exosomes and develop more efficient approaches to enhance their functions.This study aimed to explore the changes in characteristics of exosomes secreted by MSCs in periodontium in response to the matrix strain in 3D.Periodontal ligament stem cells(PDLSCs)were cultured in a 3D strain microenvironment engineered with microscale magnetically stretched collagen hydrogels.The morphology,particle distribution,marker protein expression of PDLSC-derived exosomes were analyzed.Then the pro-osteogenic property of exosomes was evaluated by assessing cell viability,proliferation,migration and osteogenic differentiation of target cells,for instance human bone marrow mesenchymal stem cells(hBMSCs).Detailed characterizations revealed that PDLSC-derived exosomes in the 3D strain mi-croenvironment were with s
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