{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T10:47:20Z","timestamp":1785840440894,"version":"3.56.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","funder":[{"name":"Mayo Clinic Transform the Practice Award"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2022,2,4]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Coronary endothelial dysfunction (CED) causes angina\/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>\n              Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1\u00d710\n              <jats:sup>5<\/jats:sup>\n              CD34+ cells\/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use\/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              Mean age was 52\u00b113 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [\u221218.0 to 32.4] to 57.6 [16.3\u201398.3]%;\n              <jats:italic>P<\/jats:italic>\n              =0.014), decreased Canadian Cardiovascular Society angina class (3.7\u00b10.5 to 1.7\u00b10.9, Wilcoxon signed-rank test,\n              <jats:italic>P<\/jats:italic>\n              =0.00018), and sublingual nitroglycerin use\/day (1 [0.4\u20133.5] to 0 [0\u20131], Wilcoxon signed-rank test,\n              <jats:italic>P<\/jats:italic>\n              =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT03471611.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.121.319644","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T10:00:29Z","timestamp":1639994429000},"page":"326-338","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":47,"title":["IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Nonobstructive Coronary Arteries"],"prefix":"10.1161","volume":"130","clinical-trial-number":[{"clinical-trial-number":"nct03471611","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Michel T.","family":"Corban","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., M.R.B., C.S.R., M.P., A.A., L.O.L., A.L.), Mayo Clinic, Rochester, MN."},{"name":"Division of Cardiology, Department of Medicine, University of Arizona College of Medicine-Tucson 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MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7934-8741","authenticated-orcid":true,"given":"Bradley R.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Biomedical Statistics and Informatics (B.R.L.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Bois","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., M.R.B., C.S.R., M.P., A.A., L.O.L., A.L.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2713-0433","authenticated-orcid":true,"given":"Rajiv","family":"Gulati","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., M.R.B., C.S.R., M.P., A.A., L.O.L., A.L.), Mayo Clinic, Rochester, 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MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2044-4664","authenticated-orcid":true,"given":"Charanjit S.","family":"Rihal","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., M.R.B., C.S.R., M.P., A.A., L.O.L., A.L.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megha","family":"Prasad","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., M.R.B., C.S.R., M.P., A.A., L.O.L., A.L.), Mayo Clinic, Rochester, MN."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9669-8009","authenticated-orcid":true,"given":"Ali","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Medicine (M.T.C., T.T., D.A., F.S., J.B., R.G., A.P., P.J.M.B., 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