title: Paracrine effect of CXCR4-overexpressing mesenchymal stem cells on ischemic heart injury.
abstract: It has been reported that CXCR4-overexpressing mesenchymal stem cells (MSCCX4) can repair heart tissue post myocardial infarction. This study aims to investigate the MSCCX4-derived paracrine cardio-protective signaling in the presence of myocardial infarction. Mesenchymal stem cells (MSCs) were divided into 3 groups: MSC only, MSCCX4, and CXCR4 gene-specific siRNA-transduced MSC. Mesenchymal stem cells were exposed to hypoxia, and then MSCs-conditioned culture medium was incubated with neonatal and adult cardiomyocytes, respectively. Cell proliferation-regulating genes were assessed by real-time polymerase chain reaction (RT-PCR). In vitro: The number of cardiomyocytes undergoing DNA synthesis, cytokinesis, and mitosis was increased to a greater extent in MSCCX4medium-treated group than control group, while this proproliferative effect was reduced in CXCR4 gene-specific siRNA-transduced MSC-treated cells. Accordingly, the maximal enhancement of vascular endothelial growth factor, cyclin 2, and transforming growth factor-β2 was observed in hypoxia-exposed MSCCX4. In vivo: MSCs were labeled with enhanced green fluorescent protein (EGFP) and engrafted into injured myocardium in rats. The number of EGFP and CD31 positive cells in the MSCCX4group was significantly increased than other 2 groups, associated with the reduced left ventricular (LV) fibrosis, the increased LV free wall thickness, the enhanced angiogenesis, and the improved contractile function. CXCR4 overexpression can mobilize MSCs into ischemic area, whereby these cells can promoted angiogenesis and alleviate LV remodeling via paracrine signaling mechanism.
authors.affiliation: Qinghai Provincial People's Hospital, Xining, Qinghai, China.
authors.forename: Shi-Zheng
authors.initials: SZ
authors.lastname: Wu
authors.affiliation: Qinghai Provincial People's Hospital, Xining, Qinghai, China.|Research Center for High Altitude Medicine, Medical College of Qinghai University, Xining, Qinghai, China.|Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Ying-Lan
authors.initials: YL
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Wen-Feng
authors.identifier: http://orcid.org/0000-0002-1499-4347
authors.initials: WF
authors.lastname: Cai
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Jialiang
authors.initials: J
authors.lastname: Liang
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Paul
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou, China.|Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Zhi-Chao
authors.initials: ZC
authors.lastname: Wu
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Meifeng
authors.initials: M
authors.lastname: Xu
authors.affiliation: Guangdong Cardiovascular Institute, Guangdong General Hospital, Guangzhou, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Pathology and Laboratory Medicine, College of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015687:Cell Hypoxia; D017077:Culture Media, Conditioned / Q000494:pharmacology; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D019899:Paracrine Communication / Q000235:genetics*; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D053781:Transforming Growth Factor beta2 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D020257:Ventricular Remodeling
chemical_list: C503722:Ccna2 protein, rat; D017077:Culture Media, Conditioned; C486264:Cxcr4 protein, rat; D056751:Cyclin A2; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D053781:Transforming Growth Factor beta2; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; C467498:vascular endothelial growth factor A, rat; D049452:Green Fluorescent Proteins
keywords: CXCR4 receptor; myocardial infarction; proliferation; stem cells