{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T22:14:26Z","timestamp":1792707266009,"version":"4.5.0"},"reference-count":37,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2017,2,17]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Studies have demonstrated that exosomes can repair cardiac tissue post\u2013myocardial infarction and recapitulate the benefits of cellular therapy.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>We evaluated the role of donor age and hypoxia of human pediatric cardiac progenitor cell (CPC)\u2013derived exosomes in a rat model of ischemia\u2013reperfusion injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>Human CPCs from the right atrial appendages from children of different ages undergoing cardiac surgery for congenital heart defects were isolated and cultured under hypoxic or normoxic conditions. Exosomes were isolated from the culture-conditioned media and delivered to athymic rats after ischemia\u2013reperfusion injury. Echocardiography at day 3 post\u2013myocardial infarction suggested statistically improved function in neonatal hypoxic and neonatal normoxic groups compared with saline-treated controls. At 28 days post\u2013myocardial infarction, exosomes derived from neonatal normoxia, neonatal hypoxia, infant hypoxia, and child hypoxia significantly improved cardiac function compared with those from saline-treated controls. Staining showed decreased fibrosis and improved angiogenesis in hypoxic groups compared with controls. Finally, using sequencing data, a computational model was generated to link microRNA levels to specific outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions<\/jats:underline>\n              :\n            <\/jats:title>\n            <jats:p>CPC exosomes derived from neonates improved cardiac function independent of culture oxygen levels, whereas CPC exosomes from older children were not reparative unless subjected to hypoxic conditions. Cardiac functional improvements were associated with increased angiogenesis, reduced fibrosis, and improved hypertrophy, resulting in improved cardiac function; however, mechanisms for normoxic neonatal CPC exosomes improved function independent of those mechanisms. This is the first study of its kind demonstrating that donor age and oxygen content in the microenvironment significantly alter the efficacy of human CPC-derived exosomes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.116.309935","type":"journal-article","created":{"date-parts":[[2016,11,22]],"date-time":"2016-11-22T03:50:17Z","timestamp":1479786617000},"page":"701-712","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":157,"title":["Experimental, Systems, and Computational Approaches to Understanding the MicroRNA-Mediated Reparative Potential of Cardiac Progenitor Cell\u2013Derived Exosomes From Pediatric Patients"],"prefix":"10.1161","volume":"120","author":[{"given":"Udit","family":"Agarwal","sequence":"first","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"George","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srishti","family":"Bhutani","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohini","family":"Ghosh-Choudhary","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua T.","family":"Maxwell","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milton E.","family":"Brown","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Mehta","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manu O.","family":"Platt","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaxuan","family":"Liang","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susmita","family":"Sahoo","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Davis","sequence":"additional","affiliation":[{"name":"From the Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta (U.A., A.G., S.B., S.G.-C., J.T.M., M.E.B., Y.M., M.O.P., M.E.D.); Division of Cardiology, Emory University School of Medicine, Atlanta, GA (U.A., J.T.M., M.E.B., M.E.D.); Children\u2019s Heart Research and Outcomes Center, Emory University School of Medicine and Children\u2019s Healthcare of Atlanta, GA (M.E.D.); and Cardiovascular Research Center, Icahn School of Medicine, Mount..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000441139.02102.80"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00687-1"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfq063"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.092627"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60195-0"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304671"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2015.06.076"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304360"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.05.068"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.305990"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.111.253286"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2014.04.006"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2354"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2015-0241"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1039\/c4lc00662c"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep07639"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2016.01.013"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.300639"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2015.02.008"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2016.01.003"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.2217\/rme.11.35"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.115.002856"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00835.2012"},{"key":"e_1_3_5_26_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01355.2006"},{"key":"e_1_3_5_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejhf.517"},{"key":"e_1_3_5_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0107556"},{"key":"e_1_3_5_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2015.05.185"},{"key":"e_1_3_5_30_2","doi-asserted-by":"publisher","DOI":"10.4238\/2015.December.29.2"},{"key":"e_1_3_5_31_2","first-page":"14500","article-title":"MicroRNA-96 promotes myocardial hypertrophy by targeting mTOR.","volume":"8","author":"Sun X","year":"2015","unstructured":"Sun X, Zhang C. 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