title: Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction.
abstract: OBJECTIVE
  We recently demonstrated that primitive neural crest-derived (NC) cells migrate from the cardiac neural crest during embryonic development and remain in the heart as dormant stem cells, with the capacity to differentiate into various cell types, including cardiomyocytes. Here, we examined the migration and differentiation potential of these cells on myocardial infarction (MI).
  
  
  RESULTS
  We obtained double-transgenic mice by crossing protein-0 promoter-Cre mice with Floxed-enhanced green fluorescent protein mice, in which the NC cells express enhanced green fluorescent protein. In the neonatal heart, NC stem cells (NCSCs) were localized predominantly in the outflow tract, but they were also distributed in a gradient from base to apex throughout the ventricular myocardium. Time-lapse video analysis revealed that the NCSCs were migratory. Some NCSCs persisted in the adult heart. On MI, NCSCs accumulated at the ischemic border zone area (BZA), which expresses monocyte chemoattractant protein-1 (MCP-1). Ex vivo cell migration assays demonstrated that MCP-1 induced NCSC migration and that this chemotactic effect was significantly depressed by an anti-MCP-1 antibody. Small NC cardiomyocytes first appeared in the BZA 2 weeks post-MI and gradually increased in number thereafter.
  
  
  CONCLUSIONS
  These results suggested that NCSCs migrate into the BZA via MCP-1/CCR2 signaling and contribute to the provision of cardiomyocytes for cardiac regeneration after MI.
authors.affiliation: Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Matsumura
authors.forename: Motoaki
authors.initials: M
authors.lastname: Sano
authors.forename: Hidenori
authors.initials: H
authors.lastname: Tabata
authors.forename: Kensuke
authors.initials: K
authors.lastname: Kimura
authors.forename: Masaki
authors.initials: M
authors.lastname: Ieda
authors.forename: Takahide
authors.initials: T
authors.lastname: Arai
authors.forename: Yohei
authors.initials: Y
authors.lastname: Ohno
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kanazawa
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Yuasa
authors.forename: Ruri
authors.initials: R
authors.lastname: Kaneda
authors.forename: Shinji
authors.initials: S
authors.lastname: Makino
authors.forename: Kazunori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Keiichi
authors.initials: K
authors.lastname: Fukuda
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D019070:Cell Lineage; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics; D019426:Integrases / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D018993:Myelin P0 Protein / Q000235:genetics; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology*; D009432:Neural Crest / Q000196:embryology*; D010960:Plasminogen Activators / Q000235:genetics; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D054390:Receptors, CCR2 / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014741:Video Recording; D051155:Wnt1 Protein / Q000235:genetics
chemical_list: C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D018993:Myelin P0 Protein; D054390:Receptors, CCR2; D051155:Wnt1 Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; C045073:Cre recombinase; D019426:Integrases; D010960:Plasminogen Activators