PMID- 21212399 OWN - NLM STAT- MEDLINE DCOM- 20110407 LR - 20110217 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 31 IP - 3 DP - 2011 Mar TI - Neural crest-derived stem cells migrate and differentiate into cardiomyocytes after myocardial infarction. PG - 582-9 LID - 10.1161/ATVBAHA.110.214726 [doi] AB - 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). METHODS AND 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. FAU - Tamura, Yuichi AU - Tamura Y AD - Department of Cardiology, Keio University School of Medicine, Tokyo, Japan. FAU - Matsumura, Keisuke AU - Matsumura K FAU - Sano, Motoaki AU - Sano M FAU - Tabata, Hidenori AU - Tabata H FAU - Kimura, Kensuke AU - Kimura K FAU - Ieda, Masaki AU - Ieda M FAU - Arai, Takahide AU - Arai T FAU - Ohno, Yohei AU - Ohno Y FAU - Kanazawa, Hideaki AU - Kanazawa H FAU - Yuasa, Shinsuke AU - Yuasa S FAU - Kaneda, Ruri AU - Kaneda R FAU - Makino, Shinji AU - Makino S FAU - Nakajima, Kazunori AU - Nakajima K FAU - Okano, Hideyuki AU - Okano H FAU - Fukuda, Keiichi AU - Fukuda K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110106 PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Ccl2 protein, mouse) RN - 0 (Ccr2 protein, mouse) RN - 0 (Chemokine CCL2) RN - 0 (Myelin P0 Protein) RN - 0 (Receptors, CCR2) RN - 0 (Wnt1 Protein) RN - 0 (enhanced green fluorescent protein) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.7.- (Cre recombinase) RN - EC 2.7.7.- (Integrases) RN - EC 3.4.21.- (Plasminogen Activators) SB - IM MH - Animals MH - *Cell Differentiation MH - *Cell Lineage MH - *Cell Movement MH - Cell Proliferation MH - Cells, Cultured MH - Chemokine CCL2/metabolism MH - Disease Models, Animal MH - Green Fluorescent Proteins/genetics MH - Integrases/genetics MH - Mice MH - Mice, Transgenic MH - Myelin P0 Protein/genetics MH - Myocardial Infarction/metabolism/*pathology MH - Myocytes, Cardiac/metabolism/*pathology MH - Neural Crest/*embryology MH - Plasminogen Activators/genetics MH - Promoter Regions, Genetic MH - RNA Interference MH - Receptors, CCR2/genetics/metabolism MH - Regeneration MH - Signal Transduction MH - Stem Cells/metabolism/*pathology MH - Time Factors MH - Video Recording MH - Wnt1 Protein/genetics EDAT- 2011/01/08 06:00 MHDA- 2011/04/08 06:00 CRDT- 2011/01/08 06:00 PHST- 2011/01/08 06:00 [entrez] PHST- 2011/01/08 06:00 [pubmed] PHST- 2011/04/08 06:00 [medline] AID - ATVBAHA.110.214726 [pii] AID - 10.1161/ATVBAHA.110.214726 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2011 Mar;31(3):582-9. doi: 10.1161/ATVBAHA.110.214726. Epub 2011 Jan 6.