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These challenges can be met by engineering an in vitro system for delivering stem cells capable of cardiac differentiation, tissue integration, and resistance to oxidative stress. In this study, we describe the formation of three\u2010dimensional (3D) cell aggregates (\u201ccardiospheres\u201d) by putative stem cells isolated from adult dog myocardium using poly\u2010<jats:sc>L<\/jats:sc>\u2010ornithine. De novo formation of cardiospheres in growth factor\u2010containing medium occurred over a period of 2\u20133 weeks, but accelerated to 2\u20133 days when seeded on poly\u2010<jats:sc>L<\/jats:sc>\u2010ornithine. Older cardiospheres developed foci of \u201cbeating\u201d cells upon co\u2010culture with rat neonatal cardiomyocytes. Cardiospheres contained cells that exhibited characteristics of undifferentiated cells; differentiating cardiomyocytes with organized contractile machinery; and vascular cells capable of forming \u201cvessel\u2010like\u201d networks. They exhibited strong resistance to elevated concentrations of hydrogen peroxide in culture and survived subcutaneous injections without undergoing neoplastic transformation up to 3 weeks post\u2010transplantation. These findings suggest that cardiospheres are potentially useful for delivering functional stem cells to the damaged heart. J. Cell. Biochem. 105: 612\u2013623, 2008. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.21862","type":"journal-article","created":{"date-parts":[[2008,7,25]],"date-time":"2008-07-25T13:53:12Z","timestamp":1216993992000},"page":"612-623","source":"Crossref","is-referenced-by-count":48,"title":["3D\u2010model of adult cardiac stem cells promotes cardiac differentiation and resistance to oxidative stress"],"prefix":"10.1002","volume":"105","author":[{"given":"T.J.","family":"Bartosh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando A.","family":"Rosales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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