{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T08:41:47Z","timestamp":1792658507137,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2016,8,19]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              The effects of c-kit\n              <jats:sup>POS<\/jats:sup>\n              cardiac progenitor cells (CPCs, and adult cell therapy in general) on left ventricular (LV) function have been regarded as modest or inconsistent.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>To determine whether 3 CPC infusions have greater efficacy than 1 infusion.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Rats with a 30-day-old myocardial infarction received 1 or 3 CPC infusions into the LV cavity, 35 days apart. Compared with vehicle-treated rats, the single-dose group exhibited improved LV function after the first infusion (consisting of CPCs) but not after the second and third (vehicle). In contrast, in the multiple-dose group, regional and global LV function improved by a similar degree after each CPC infusion, resulting in greater cumulative effects. For example, the total increase in LV ejection fraction was approximately triple in the multiple-dose group versus the single-dose group (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). The multiple-dose group also exhibited more viable tissue and less scar, less collagen in the risk and noninfarcted regions, and greater myocyte density in the risk region.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>This is the first demonstration that repeated CPC administrations are markedly more effective than a single administration. The concept that the full effects of CPCs require repeated doses has significant implications for both preclinical and clinical studies; it suggests that the benefits of cell therapy may be underestimated or even overlooked if they are measured after a single dose, and that repeated administrations are necessary to evaluate the effectiveness of a cell product properly. In addition, we describe a new method that enables studies of repeated cell administrations in rodents.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.308937","type":"journal-article","created":{"date-parts":[[2016,7,1]],"date-time":"2016-07-01T00:51:04Z","timestamp":1467334264000},"page":"635-651","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":118,"title":["Repeated Administrations of Cardiac Progenitor Cells Are Markedly More Effective Than a Single Administration"],"prefix":"10.1161","volume":"119","author":[{"given":"Yukichi","family":"Tokita","sequence":"first","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xian-Liang","family":"Tang","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianhong","family":"Li","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Wysoczynski","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung U.","family":"Hong","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunichi","family":"Nakamura","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Xie","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding","family":"Li","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular Cardiology, University of Louisville, KY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg","family":"Hunt","sequence":"additional","affiliation":[{"name":"From the Division of Cardiovascular Medicine, Institute of Molecular 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