title: CXCR4 receptor overexpression in mesenchymal stem cells facilitates treatment of acute lung injury in rats.
abstract: Novel therapeutic regimens for tissue renewal incorporate mesenchymal stem cells (MSCs) as they differentiate into a variety of cell types and are a stem cell type that is easy to harvest and to expand in vitro. However, surface chemokine receptors, such as CXCR4, which are involved in the mobilization of MSCs, are expressed only on the surface of a small proportion of MSCs, and the lack of CXCR4 expression may underlie the low efficiency of homing of MSCs toward tissue damage, which results in a poor curative effect. Here, a rat CXCR4 expressing lentiviral vector was constructed and introduced into MSCs freshly prepared from rat bone marrow. The influence of CXCR4 expression on migration, proliferation, differentiation, and paracrine effects of MSCs was examined in vitro. The in vivo properties of CXCR4-MSCs were also investigated in a model of acute lung injury in rats induced by lipopolysaccharide. Expression of CXCR4 in MSCs significantly enhanced the chemotactic and paracrine characteristics of the cells in vitro but did not affect self-renewal or differentiation into alveolar and vascular endothelial cells. In vivo, CXCR4 improved MSC homing and colonization of damaged lung tissue, and furthermore, the transplanted CXCR4-MSCs suppressed the development of acute lung injury in part by modulating levels of inflammatory molecules and the neutrophil count. These results indicated that efficient mobilization of MSCs to sites of tissue injury may be due to CXCR4, and therefore, increased expression of CXCR4 may improve their therapeutic potential in the treatment of diseases where tissue damage develops.
authors.affiliation: From the School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Jing-Xian
authors.initials: JX
authors.lastname: Yang
authors.affiliation: From the School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China, School of Pharmacy, China Medical University, Shenyang 110013, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital, Dalian Medical University, Dalian 116011, China, and.
authors.forename: Han-Wei
authors.initials: HW
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Dalian Medical University, Dalian 116044, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Gao
authors.affiliation: From the School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Yang
authors.affiliation: First Affiliated Hospital, Dalian Medical University, Dalian 116011, China, and wenqp050607@gmail.com.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Wen
mesh_terms: D055371:Acute Lung Injury / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002633:Chemotaxis; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007249:Inflammation; D016086:Lentivirus; D008070:Lipopolysaccharides / Q000737:chemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051381:Rats; D019718:Receptors, CXCR4 / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: C486264:Cxcr4 protein, rat; D008070:Lipopolysaccharides; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins
keywords: Cell Migration; Lung Injury; Mesenchymal Stem Cells (MSCs); Migration; Transplantation