title: Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia.
abstract: : Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton's jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia.
  
  
  
  Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called "no-option" patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation.
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Chuan-Bin
authors.initials: CB
authors.lastname: Liu
authors.affiliation: Department of Anesthesia, Xinqiao Hospital, Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Ivy Institute of Stem Cells Company Limited, Beijing, People's Republic of China.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: Ivy Institute of Stem Cells Company Limited, Beijing, People's Republic of China.
authors.forename: Shi-Ze
authors.initials: SZ
authors.lastname: Ma
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: An-Heng
authors.initials: AH
authors.lastname: Liu
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Jin-Hui
authors.initials: JH
authors.lastname: Fu
authors.affiliation: Ivy Institute of Stem Cells Company Limited, Beijing, People's Republic of China.
authors.forename: Yu-Qian
authors.initials: YQ
authors.lastname: Liang
authors.affiliation: 307-Ivy Translational Medicine Center, Laboratory of Oncology, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China.
authors.forename: Bing
authors.initials: B
authors.lastname: Liu
authors.affiliation: Ivy Institute of Stem Cells Company Limited, Beijing, People's Republic of China.
authors.forename: Dong-Ying
authors.initials: DY
authors.lastname: Wu
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China xiaozhong__zhang@126.com lvsh2005@163.com.
authors.forename: Shuang-Hong
authors.initials: SH
authors.lastname: Lü
authors.affiliation: Department of Cardiovascular Medicine, Affiliated Hospital of Academy of Military Medical Sciences, Beijing, People's Republic of China xiaozhong__zhang@126.com lvsh2005@163.com.
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Zhang
mesh_terms: D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D003097:Collateral Circulation; D003326:Coronary Circulation; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005355:Fibrosis; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic; D010641:Phenotype; D020127:Recovery of Function; D013318:Stroke Volume; D013552:Swine; D013997:Time Factors; D014470:Umbilical Cord / Q000166:cytology*; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling; D059631:Wharton Jelly / Q000166:cytology*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D016207:Cytokines; D014841:von Willebrand Factor
keywords: Chronic myocardial ischemia; Ischemic heart disease; Mesenchymal stromal cells; Umbilical cord; Ventricular remodeling