title: Stromal cell-derived factor-1-directed bone marrow mesenchymal stem cell migration in response to inflammatory and/or hypoxic stimuli.
abstract: Directing cell trafficking toward a target site of interest is critical for advancing stem cell therapy in clinical theranostic applications. In this study, we investigated the effects of inflammatory and/or hypoxic stimuli on the migration of bone marrow mesenchymal stem cells (BMMSCs) during in vitro culture and after in vivo implantation. Using tablet scratch experiments and observations from a transwell system, we found that both inflammatory and hypoxic stimuli significantly enhanced cell migration. However, the combination of inflammatory and hypoxic stimuli did not result in a synergistic effect. The presence of stromal cell-derived factor-1 (SDF-1) significantly enhanced cell migration irrespective of the incubation conditions, and these positive effects could be blocked by treatment with AMD3100. Based on a time course experiment, we found that preconditioning cells with either inflammatory or hypoxic stimuli for 24 h or with both stimuli for 12 h led to high levels of chemokine receptor type 4 (CXCR4) expression. In vivo studies further demonstrated that pretreatment of BMMSCs with inflammatory and/or hypoxic stimuli resulted in an increased number of systemically injected cells migrating toward skin injuries, and local SDF-1 administration significantly increased cell migration. These findings suggest that in vitro control of either inflammatory or hypoxic stimuli has significant potential to enhance SDF-1-directed BMMSC migration via the upregulation of CXCR4 expression. Although combining the stimuli did not necessarily lead to a synergistic effect, the potential to reduce the dose and time required for cell preconditioning indicates that combinations of various strategies warrant further exploration.
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Rui-Xin
authors.initials: RX
authors.lastname: Wu
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Gao
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Xia
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Hao-Ning
authors.initials: HN
authors.lastname: Tang
authors.affiliation: a State Key Laboratory of Military Stomatology, Department of Periodontology, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.|b Shaanxi Key Laboratory of Stomatology, Biomaterials Unit, School of Stomatology, Fourth Military Medical University , Xi'an , P. R., China.
authors.forename: Fa-Ming
authors.initials: FM
authors.lastname: Chen
mesh_terms: D001854:Bone Marrow Cells / Q000166:cytology*; D015687:Cell Hypoxia / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D002469:Cell Separation; D054377:Chemokine CXCL12 / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008954:Models, Biological; D019718:Receptors, CXCR4 / Q000378:metabolism; D012867:Skin / Q000473:pathology; D013997:Time Factors
chemical_list: C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: cell migration; chemokine receptor type 4; hypoxia; inflammation; mesenchymal stem cells; stromal cell-derived factor-1