title: Cell surface engineering to enhance mesenchymal stem cell migration toward an SDF-1 gradient.
abstract: Mesenchymal stem cell (MSC) therapy for the treatment of myocardial infarction (MI) has shown considerable promise in clinical trials. A billion MSCs need to be administered for therapeutic efficacy, however, because only ∼1% of the cells reach the ischemic myocardium after systemic infusion. This is due to the loss of the homing signal on the surface of the MSCs during their expansion in culture. Stromal-derived factor-1 (SDF-1) is up-regulated immediately after infarction and is released into the peripheral blood. This SDF-1 reaches the bone marrow and recruits CXC chemokine receptor 4 (CXCR4)-positive stem cells. The CXCR4/SDF-1 axis plays an important role in MSC homing to the ischemic myocardium. Since SDF-1 is highly expressed for only 48 h after infarction, the current approaches requiring long-term culture of MSCs to induce CXCR4 expression are not clinically useful. To provide a clinically viable means to improve the homing of MSCs, we have developed a surface modification method to incorporate recombinant CXCR4 protein on the membrane of MSCs within 10 min. Using this method, we have confirmed the improved migration of MSCs toward an SDF-1 gradient.
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Amit N
authors.initials: AN
authors.lastname: Patel
authors.affiliation: Division of Cardiothoracic Surgery, Department of Surgery, University of Utah School of Medicine, Salt Lake City, UT, USA. Electronic address: david.bull@hsc.utah.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Bull
mesh_terms: D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation / Q000502:physiology; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D009203:Myocardial Infarction / Q000628:therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D011092:Polyethylene Glycols
keywords: CXCR4; Mesenchymal stem cell; Myocardial infarction; SDF-1