{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T07:19:05Z","timestamp":1792653545423,"version":"4.5.0"},"reference-count":65,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2024,8,27]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Exosome therapy shows potential for cardiac repair after injury. However, intrinsic challenges such as short half-life and lack of clear targets hinder the clinical feasibility. Here, we report a noninvasive and repeatable method for exosome delivery through inhalation after myocardial infarction (MI), which we called stem cell\u2013derived exosome nebulization therapy (SCENT).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>Stem cell\u2013derived exosomes were characterized for size distribution and surface markers. C57BL\/6 mice with MI model received exosome inhalation treatment through a nebulizer for 7 consecutive days. Echocardiographies were performed to monitor cardiac function after SCENT, and histological analysis helped with the investigation of myocardial repair. Single-cell RNA sequencing of the whole heart was performed to explore the mechanism of action by SCENT. Last, the feasibility, efficacy, and general safety of SCENT were demonstrated in a swine model of MI, facilitated by 3-dimensional cardiac magnetic resonance imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      Recruitment of exosomes to the ischemic heart after SCENT was detected by ex vivo IVIS imaging and fluorescence microscopy. In a mouse model of MI, SCENT ameliorated cardiac repair by improving left ventricular function, reducing fibrotic tissue, and promoting cardiomyocyte proliferation. Mechanistic studies using single-cell RNA sequencing of mouse heart after SCENT revealed a downregulation of\n                      <jats:italic toggle=\"yes\">Cd36<\/jats:italic>\n                      in endothelial cells (ECs). In an EC-\n                      <jats:italic toggle=\"yes\">Cd36<\/jats:italic>\n                      <jats:sup>fl\/\u2212<\/jats:sup>\n                      conditional knockout mouse model, the inhibition of CD36, a fatty acid transporter in ECs, led to a compensatory increase in glucose utilization in the heart and higher ATP generation, which enhanced cardiac contractility. In pigs, cardiac magnetic resonance imaging showed an enhanced ejection fraction (\u0394=11.66\u00b15.12%) and fractional shortening (\u0394=5.72\u00b12.29%) at day 28 after MI by SCENT treatment compared with controls, along with reduced infarct size and thickened ventricular wall.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>\n                      In both rodent and swine models, our data proved the feasibility, efficacy, and general safety of SCENT treatment against acute MI injury, laying the groundwork for clinical investigation. Moreover, the EC-\n                      <jats:italic toggle=\"yes\">Cd36<\/jats:italic>\n                      <jats:sup>fl\/\u2212<\/jats:sup>\n                      mouse model provides the first in vivo evidence showing that conditional EC-CD36 knockout can ameliorate cardiac injury. Our study introduces a noninvasive treatment option for heart disease and identifies new potential therapeutic targets.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.123.065005","type":"journal-article","created":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T14:00:52Z","timestamp":1724680852000},"page":"710-723","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":133,"title":["Inhalable Stem Cell Exosomes Promote Heart Repair After Myocardial Infarction"],"prefix":"10.1161","volume":"150","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5739-5168","authenticated-orcid":true,"given":"Junlang","family":"Li","sequence":"first","affiliation":[{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (J.L., Y.L., Y.L., Z.W.)."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh (J.L., Y.L., K.H., Y.L., Z.W., H.J.L., K.D.P., P.-U.C.D.)."},{"name":"Xsome Biotech Inc, Raleigh, NC (J.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4339-2716","authenticated-orcid":true,"given":"Shenghuan","family":"Sun","sequence":"additional","affiliation":[{"name":"Bakar Computational Health Sciences Institute, University of California, San Francisco (S.S., A.J.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4645-5786","authenticated-orcid":true,"given":"Dashuai","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering (D.Z., S.L., S.H., K.C.), Columbia University, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1190-0800","authenticated-orcid":true,"given":"Xuan","family":"Mei","sequence":"additional","affiliation":[{"name":"Division of Engineering in Medicine, Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School, Cambridge, MA (X.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbo","family":"Lyu","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (J.L., Y.L., Y.L., Z.W.)."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh (J.L., Y.L., K.H., Y.L., Z.W., H.J.L., K.D.P., P.-U.C.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9355-7224","authenticated-orcid":true,"given":"Ke","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh (J.L., Y.L., K.H., Y.L., Z.W., H.J.L., K.D.P., P.-U.C.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1929-5465","authenticated-orcid":true,"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (J.L., Y.L., Y.L., Z.W.)."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh (J.L., Y.L., K.H., Y.L., Z.W., H.J.L., K.D.P., P.-U.C.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2969-5876","authenticated-orcid":true,"given":"Shuo","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering (D.Z., S.L., S.H., K.C.), Columbia University, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5245-6726","authenticated-orcid":true,"given":"Zhenzhen","family":"Wang","sequence":"additional","affiliation":[{"name":"Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University (J.L., Y.L., Y.L., Z.W.)."},{"name":"Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh (J.L., Y.L., K.H., Y.L., Z.W., H.J.L., K.D.P., P.-U.C.D.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8570-3439","authenticated-orcid":true,"given":"Shiqi","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering (D.Z., S.L., S.H., K.C.), Columbia University, New York, NY."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6364-7627","authenticated-orcid":true,"given":"Halle 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