Neural Crest-Derived Stem Cells Migrate and Differentiate Into Cardiomyocytes After Myocardial Infarction

Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 03/2011; 31(3):582-9. DOI: 10.1161/ATVBAHA.110.214726
Source: PubMed


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).
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.
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.

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    • "In the healthy heart, neural-crest derived (GFP+) cardiomyocytes were undetectable during the first week after birth but appeared at 2 weeks postnatally and increased in number thereafter; however, their absolute contributions to the myocyte pool were minimal (∼0.3% GFP+ cardiomyocytes in the septum, < 0.1% GFP+ cardiomyocytes in the rest of the left ventricle). After myocardial infarction, small GFP+ cardiomyocytes (presumably arising from differentiation of neural-crest-derived cells) first appeared in the border zone 2 weeks post-injury and gradually increased in number thereafter (comprising 3% of total cardiomyocytes in the border zone at 12 weeks post-injury).33 While this study is limited by the fact that the activity of Cre-recombinase was not temporally controlled in an inducible manner (and thus spontaneous activation of the protein-0 promoter in resident cardiomyocytes would result in GFP labeling) it suggests that progenitor cells may contribute to generation of new myocytes (especially post-injury). "
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    09/2013; 2013(3):303-315. DOI:10.5339/gcsp.2013.37
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    • "Recently, lineage mapping has been utilized to locate niches in animal models by genetically labeling SC markers and identifying their location in adult tissue.78,79 An example of lineage mapping is the recent study of Tamura et al78 of neural crest-derived SCs found in the heart that migrate and differentiate into cardiomyocytes after MI. The lineage mapping has been utilized for locating SC niches in a variety of developing organisms.79 "
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    • "Previous studies have shown that non-hematocrit-inducing EPO derivatives can also directly protect cardiomyocytes from apoptosis (Ueba et al., 2010). EPO treatment also induced CCL2 promoter activity in cardiomyocytes and, because CCL2 can protect cardiomyocytes from apoptosis (Tarzami et al., 2005) and promote regeneration of cardiomyocytes by inducing migration of neuronal crest cells into the injured heart (Tamura et al., 2011), the link between EPO and CCL2 signaling may be beneficial not only for the cardiac vasculature but also for other cardiac cells. The cardioprotective effect seen with CERA treatment in the two mouse models that we studied could therefore be multifaceted. "
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