{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T13:28:51Z","timestamp":1792589331685,"version":"4.5.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,3,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Induced pluripotent stem cells and their differentiated cardiomyocytes (\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      s) have tremendous potential as patient\u2010specific therapy for ischemic cardiomyopathy following myocardial infarctions, but difficulties in viable transplantation limit clinical translation. Exosomes secreted from\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      s (iCM\u2010Ex) can be robustly collected in vitro and injected in lieu of live\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      s as a cell\u2010free therapy for myocardial infarction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex were precipitated from\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      supernatant and characterized by protein marker expression, nanoparticle tracking analysis, and functionalized nanogold transmission electron microscopy.\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex were then used in in vitro and in vivo models of ischemic injuries. Cardiac function in vivo was evaluated by left ventricular ejection fraction and myocardial viability measurements by magnetic resonance imaging. Cardioprotective mechanisms were studied by\n                      <jats:styled-content style=\"fixed-case\">JC<\/jats:styled-content>\n                      \u20101 (tetraethylbenzimidazolylcarbocyanine iodide) assay, immunohistochemistry, quantitative real\u2010time polymerase chain reaction, transmission electron microscopy, and immunoblotting.\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex measured \u2248140\u00a0nm and expressed\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      63 and\n                      <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                      9.\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      and\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex micro\n                      <jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\n                      profiles had significant overlap, indicating that exosomal content was reflective of the parent cell. Mice treated with\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex demonstrated significant cardiac improvement post\u2013myocardial infarction, with significantly reduced apoptosis and fibrosis. In vitro\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      apoptosis was significantly reduced by hypoxia and exosome biogenesis inhibition and restored by treatment with\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex or rapamycin. Autophagosome production and autophagy flux was upregulated in\n                      <jats:styled-content style=\"fixed-case\">iCM<\/jats:styled-content>\n                      \u2010Ex groups in vivo and in vitro.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">iCM\u2010Ex improve post\u2013myocardial infarction cardiac function by regulating autophagy in hypoxic cardiomyoytes, enabling a cell\u2010free, patient\u2010specific therapy for ischemic cardiomyopathy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.119.014345","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T05:00:18Z","timestamp":1583384418000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":122,"title":["Exosomes From Induced Pluripotent Stem Cell\u2013Derived Cardiomyocytes Promote Autophagy for Myocardial Repair"],"prefix":"10.1161","volume":"9","author":[{"given":"Michelle R.","family":"Santoso","sequence":"first","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gentaro","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Tada","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji\u2010Hye","family":"Jung","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya","family":"Vaskova","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond G.","family":"Sierra","sequence":"additional","affiliation":[{"name":"Hard X\u2010ray Department LCLS SLAC National Accelerator Laboratory Menlo Park CA"},{"name":"Stanford PULSE Institute SLAC National Accelerator Laboratory Menlo Park CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelius","family":"Gati","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew B.","family":"Goldstone","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery Falk Building Stanford University Medical Center Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"von Bornstaedt","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Shukla","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Wu","sequence":"additional","affiliation":[{"name":"Stanford Cardiovascular Institute Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichi","family":"Wakatsuki","sequence":"additional","affiliation":[{"name":"Department of Structural Biology Stanford University School of Medicine Stanford CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y. 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