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oai:repisalud.isciii.es:20.500.12105/228732024-09-13T09:11:47Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Antich-Rosselló, Miquel author Forteza-Genestra, Maria Antónia author Calvo, J author Gayà, Antoni author Monjo, M author Ramis, Joana Maria author 2020-10 Aims: Platelet concentrates, like platelet-rich plasma (PRP) and platelet lysate (PL), are widely used in regenerative medicine, especially in bone regeneration. However, the lack of standard procedures and controls leads to high variability in the obtained results, limiting their regular clinical use. Here, we propose the use of platelet-derived extracellular vesicles (EVs) as an off-the-shelf alternative for PRP and PL for bone regeneration. In this article, we evaluate the effect of PL-derived EVs on the biocompatibility and differentiation of mesenchymal stromal cells (MSCs). Methods: EVs were obtained first by ultracentrifugation (UC) and then by size exclusion chromatography (SEC) from non-activated PL. EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and the expression of CD9 and CD63 markers by western blot. The effect of the obtained EVs on osteoinduction was evaluated in vitro on human umbilical cord MSCs by messenger RNA (mRNA) expression analysis of bone markers, alkaline phosphatase activity (ALP), and calcium (Ca2+) content. Results: Osteogenic differentiation of MSCs was confirmed when treated with UC-isolated EVs. In order to disprove that the effect was due to co-isolated proteins, EVs were isolated by SEC. Purer EVs were obtained and proved to maintain the differentiation effect on MSCs and showed a dose-dependent response. Conclusion: PL-derived EVs present an osteogenic capability comparable to PL treatments, emerging as an alternative able to overcome PL and PRP limitations. Antich Rosselló M, Forteza Genestra MA, Calvo J, Gaya A, Monjo M, Ramis JM. Platelet-derived extracellular vesicles promote osteoinduction of mesenchymal stromal cells. Bone Jt Res. 2020 Oct;9(10):667-74. 10.1302/2046-3758.910.BJR-2020-0111.R2 2046-3758 Bone & Joint Research http://hdl.handle.net/20.500.13003/17238 33101656 L2008457764 2-s2.0-85095570814 https://hdl.handle.net/20.500.12105/22873 585211100004 Extracellular vesicles Mesenchymal stromal cells Platelet lysate Platelet-derived extracellular vesicles promote osteoinduction of mesenchymal stromal cells