Extracellular Vesicles Derived from Osteogenically Induced Human Bone Marrow Mesenchymal Stem Cells Can Modulate Lineage Commitment

• Published in: Stem cell reports 2016-03, Vol.6 (3), p.284-291
• Main Authors: Martins, Margarida, Ribeiro, Diana, Martins, Albino, Reis, Rui Luís, Neves, Nuno Meleiro
• Format: Article
• Language: English
• Subjects: Aged; Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Bone Morphogenetic Protein 2 - genetics; Bone Morphogenetic Protein 2 - metabolism; Cell Lineage; Cells, Cultured; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Extracellular Vesicles - metabolism; Humans; Integrin-Binding Sialoprotein - genetics; Integrin-Binding Sialoprotein - metabolism; Mesenchymal Stromal Cells - metabolism; Middle Aged; Osteogenesis; Osteopontin - genetics; Osteopontin - metabolism
• ISSN: 2213-6711; 2213-6711
• DOI: 10.1016/j.stemcr.2016.01.001

The effective osteogenic commitment of human bone marrow mesenchymal stem cells (hBMSCs) is critical for bone regenerative therapies. Extracellular vesicles (EVs) derived from hBMSCs have a regenerative potential that has been increasingly recognized. Herein, the osteoinductive potential of osteogenically induced hBMSC-EVs was examined. hBMSCs secreted negatively charged nanosized vesicles (∼35 nm) with EV-related surface markers. The yield of EVs over 7 days was dependent on an osteogenic stimulus (standard chemical cocktail or RUNX2 cationic-lipid transfection). These EVs were used to sequentially stimulate homotypic uncommitted cells during 7 days, matching the seeding density of EV parent cells, culture time, and stimuli. Osteogenically committed hBMSC-EVs induced an osteogenic phenotype characterized by marked early induction of BMP2, SP7, SPP1, BGLAP/IBSP, and alkaline phosphatase. Both EV groups outperformed the currently used osteoinductive strategies. These data show that naturally secreted EVs can guide the osteogenic commitment of hBMSCs in the absence of other chemical or genetic osteoinductors. [Display omitted] •hBMSC-EV secretion during culture is osteogenic stimulus dependent•Osteogenically induced hBMSC-EVs are early osteoinductors•Osteogenically induced hBMSC-EVs outperform currently used osteoinductive strategies In this article, Neves and colleagues show that hBMSCs secrete populations of nanosized EVs during the osteogenic commitment induced either by standard osteogenic medium or by Runx-2 transfection. Furthermore, the EVs obtained during both hBMSC osteogenic induction methods carry potent signals that are efficient in driving the osteogenic lineage progression of homotypic cells.