title: Enhancing the migration ability of mesenchymal stromal cells by targeting the SDF-1/CXCR4 axis.
abstract: Mesenchymal stromal cells (MSCs) are currently being investigated in numerous clinical trials of tissue repair and various immunological disorders based on their ability to secrete trophic factors and to modulate inflammatory responses. MSCs have been shown to migrate to sites of injury and inflammation in response to soluble mediators including the chemokine stromal cell-derived factor-(SDF-)1, but during in vitro culture expansion MSCs lose surface expression of key homing receptors particularly of the SDF-1 receptor, CXCR4. Here we review studies on enhancement of SDF-1-directed migration of MSCs with the premise that their improved recruitment could translate to therapeutic benefits. We describe our studies on approaches to increase the CXCR4 expression in in vitro-expanded cord blood-derived MSCs, namely, transfection, using the commercial liposomal reagent IBAfect, chemical treatment with the histone deacetylase inhibitor valproic acid, and exposure to recombinant complement component C1q. These methodologies will be presented in the context of other cell targeting and delivery strategies that exploit pathways involved in MSC migration. Taken together, these findings indicate that MSCs can be manipulated in vitro to enhance their in vivo recruitment and efficacy for tissue repair.
authors.affiliation: Canadian Blood Services, Research and Development, Edmonton, AB, Canada.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Marquez-Curtis
authors.affiliation: Canadian Blood Services, Research and Development, Edmonton, AB, Canada ; Department of Medicine, University of Alberta, CBS Building, 8249-114 Street NW, Edmonton, AB, Canada T6G 2R8.
authors.forename: Anna
authors.initials: A
authors.lastname: Janowska-Wieczorek
mesh_terms: D002454:Cell Differentiation; D002465:Cell Movement / Q000235:genetics*; D054377:Chemokine CXCL12 / Q000096:biosynthesis* / Q000235:genetics; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4