title: Reconstitute the damaged heart via the dual reparative roles of pericardial adipose-derived flk-1+ stem cells.
abstract: BACKGROUND
  The pericardial adipose derived stromal cells (pADSC) own a developmental origin from the "second heart field" and thus favor myogenic differentiation. The present experiments extended our previous observation by defining a subset of pADSC marked with the expression of flk-1, a type II receptor for VEGF to efficiently enhance cardiac repair.
  
  
  RESULTS
  Immunofluorescence and flow cytometry showed that flk-1 positive cells represented about 12% in the pericardial tissue and the total isolated pADSC. The purified flk-1 positive pADSC by magnetic sorting (flk-1pospADSC) show the ability of forming spherical structure in which both myogenic (cTnT+) and angiogenic (vWF+) precursors were concurrently generated in culture. After being intramyocardially transplanted into the ischemic hearts, flk-1pospADSC yielded superior structural repair to PBS control or flk-1negpADSC, characterized by the thickening of the infarcted wall in which both myogenesis and angiogenesis of microvasculature (preferentially with ϕ<50 μm) were significantly ensured (p<0.01). The structure benefits were also translated into a functional restoration 28 days after transplantation (EF=44% vs. 62%, p<0.01). Further pulse-chase labeling experiments with BrdU revealed that neomyogenesis and neoangiogenesis contribute in the structural repair. The newly formed myocardium was resulted from the proliferation of pre-existing cardiomyocytes that re-entered cell cycle (ki-67 positive).
  
  
  CONCLUSIONS
  Flk-1pospADSC are capable of concurrently giving rise to both myogenic and angiogenic precursors in vitro and, after transplantation in vivo, to reconstitute the damaged heart by the neoformation of microvasculature and of cardiomyocytes and thus represent an attracting donor cells for stem cell-based therapy.
authors.affiliation: Department of Cardiac Surgery, Zhejiang Hospital, Lingyin Rd. 12, 310013 Hangzhou, China. Electronic address: wxm216@sina.com.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Danyang People's Hospital, West Xinmin Rd. 5, 212300 Danyang, China. Electronic address: drylxq@163.com.
authors.forename: Xueqing
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiothoracic and Operation Theater, Zhejiang Provincial People's Hospital, Shangtang Rd. 158, 310014 Hangzhou, China. Electronic address: zhhui1025@sina.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic and Operation Theater, Zhejiang Provincial People's Hospital, Shangtang Rd. 158, 310014 Hangzhou, China. Electronic address: norway2256@gmail.com.
authors.forename: Liangming
authors.initials: L
authors.lastname: Nie
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, XueFu Rd. 301, Zhenjiang, China. Electronic address: chenmina88@yahoo.com.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Institute of Molecular Cardiology, Heinrich-Heine University of Düsseldorf, Moorenstr. 5, 40225 Düsseldorf, Germany. Electronic address: ding@uni-duesseldorf.de.
authors.forename: Zhaoping
authors.initials: Z
authors.lastname: Ding
mesh_terms: D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000628:therapy*; D010496:Pericardium / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Adipose-derived stromal cells; Microvasculature; Myogenesis; Pericardial; Vasculogenesis; flk-1