title: Placental Growth Factor Promotes Cardiac Muscle Repair via Enhanced Neovascularization.
abstract: OBJECTIVE
  Transplantation of mesenchymal stem cells (MSCs) improves post-injury cardiac muscle repair using ill-defined mechanisms. Recently, we have shown that production and secretion of placental growth factor (PLGF) by MSCs play a critical role in the MSCs-mediated post-injury cardiac muscle repair. In this study, we addressed the underlying molecular mechanisms, focusing specifically on the interactions between MSCs, macrophages and endothelial cells.
  
  
  METHODS
  We isolated macrophages (BM-MΦ) from mouse bone-marrow derived cells based on F4/80 expression by flow cytometry. BM-MΦ were treated with different doses of PLGF. Cell number was analyzed by a MTT assay. Macrophage polarization was examined based on CD206 expression by flow cytometry. PLGF levels in macrophage subpopulations were analyzed by RT-qPCR and ELISA. Effects of macrophages on vascularization were evaluated by a collagen gel assay using Human umbilical vein endothelial cells (HUVECs) co-cultured with PLGF-treated macrophages.
  
  
  RESULTS
  PLGF did not increase macrophage number, but dose-dependently polarized macrophages into a M2 subpopulation. M2 macrophages expressed high levels of PLGF. PLGF-polarized M2 macrophages significantly increased tubular structures in the collagen gel assay.
  
  
  CONCLUSIONS
  Our data suggest that MSCs-derived PLGF may induce macrophage polarization into a M2 subpopulation, which in turn releases more PLGF to promote local neovascularization for augmenting post-injury cardiac muscle repair. This study thus sheds novel light on the role of PLGF in cardiac muscle regeneration.
authors.affiliation: Department of Cardiac Surgery, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Anqing
authors.initials: A
authors.lastname: Chen
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Wu
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000235:genetics / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003094:Collagen / Q000737:chemistry; D005782:Gels; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016130:Immunophenotyping; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D061251:Primary Cell Culture; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism
chemical_list: D000943:Antigens, Differentiation; D005782:Gels; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; C000608036:PGF protein, human; C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D011956:Receptors, Cell Surface; C036763:monocyte-macrophage differentiation antigen; D000072483:Placenta Growth Factor; D003094:Collagen