title: Mesenchymal stromal cells regulate the cell mobility and the immune response during osteogenesis through secretion of vascular endothelial growth factor A.
abstract: Cell-cell interaction is believed to play a critical role in the cell-based therapy for bone regeneration. However, the mechanisms involved in the interaction between donor cells and host cells during the bone healing process are still not clear. This study investigated the potential effect of vascular endothelial growth factor A (VEGFA) produced by osteogenically differentiated mesenchymal stem cells (O-MSCs) on the recruitment and regulation of undifferentiated MSCs and macrophages during osteogenesis. Factors secreted from MSCs during osteogenic differentiation were monitored by cytokine arrays. Indirect coculture models were applied to study the effect of VEGFA derived from O-MSCs on the motility, cell morphology and CXCL12/CXCR4 expression in MSCs as well as the regulation of local immune response. A mouse skull defect model was used to unveil the cell recruitment, macrophage activity and new bone formation following O-MSCs transplantation. It was found that VEGFA secretion increased dramatically during the osteogenic differentiation of MSCs. The secreted VEGFA by O-MSCs stimulated the expression of CXCL12/CXCR4, resulting in the recruitment of MSCs and macrophages to the bone defects. It was noted that O-MSCs could regulate the local inflammation by modulating the expression of proinflammatory cytokines in macrophages and neutralizing VEGFA produced by O-MSCs resulted in significant decrease of cell recruitment, cytokine secretion and new bone formation. This study demonstrates that VEGFA secreted by O-MSCs plays a pivotal role in the cell recruitment and regulation of local immune response during osteogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Wei
authors.initials: W
authors.lastname: Fan
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Indira
authors.initials: I
authors.lastname: Prasadam
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.|The Prince Charles Hospital, Brisbane, Queensland, Australia.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.|Australia-China Centre for Tissue Engineering and Regenerative Medicine (ACCTERM), Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000368:Aged; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D054377:Chemokine CXCL12 / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005260:Female; D006801:Humans; D007109:Immunity / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D010012:Osteogenesis / Q000187:drug effects; D000067996:RAW 264.7 Cells; D019718:Receptors, CXCR4 / Q000378:metabolism; D012886:Skull / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D057134:Antibodies, Neutralizing; D054377:Chemokine CXCL12; D017077:Culture Media, Conditioned; D018836:Inflammation Mediators; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A
keywords: VEGF; bone; cell migration; immunoregulation; macrophages; mesenchymal stem cells; osteoblasts