Transplantation of Human Umbilical Cord Blood–Derived Cellular Fraction Improves Left Ventricular Function and Remodeling After Myocardial Ischemia/Reperfusion

• Published in: Circulation research Vol. 125; no. 8; pp. 759 - 772
• Main Authors: Zhao, Lin, Cheng, Guangming, Choksi, Kashyap, Samanta, Anweshan, Girgis, Magdy, Soder, Rupal, Vincent, Robert J, Wulser, Michael, De Ruyter, Matt, McEnulty, Patrick, Hauptman, Jeryl, Yang, Yanjuan, Weiner, Carl P, Dawn, Buddhadeb
• Format: Journal Article
• Language: English
• Published: American Heart Association, Inc 27.09.2019
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/CIRCRESAHA.119.315216

RATIONALE:Human umbilical cord blood (hUCB) contains diverse populations of stem/progenitor cells. Whether hUCB-derived nonhematopoietic cells would induce cardiac repair remains unknown. OBJECTIVE:To examine whether intramyocardial transplantation of hUCB-derived CD45Lin nonhematopoietic cellular fraction after a reperfused myocardial infarction in nonimmunosuppressed rats would improve cardiac function and ameliorate ventricular remodeling. METHODS AND RESULTS:Nonhematopoietic CD45Lin cells were isolated from hUCB. Flow cytometry and quantitative polymerase chain reaction were used to characterize this subpopulation. Age-matched male Fischer 344 rats underwent a 30-minute coronary occlusion followed by reperfusion and 48 hours later received intramyocardial injection of vehicle or hUCB CD45Lin cells. After 35 days, compared with vehicle-treated rats, CD45Lin cell–treated rats exhibited improved left ventricular function, blunted left ventricular hypertrophy, greater preservation of viable myocardium in the infarct zone, and superior left ventricular remodeling. Mechanistically, hUCB CD45Lin cell injection favorably modulated molecular pathways regulating myocardial fibrosis, cardiomyocyte apoptosis, angiogenesis, and inflammation in postinfarct ventricular myocardium. Rare persistent transplanted human cells could be detected at both 4 and 35 days after myocardial infarction. CONCLUSIONS:Transplantation of hUCB-derived CD45Lin nonhematopoietic cellular subfraction after a reperfused myocardial infarction in nonimmunosuppressed rats ameliorates left ventricular dysfunction and improves remodeling via favorable paracrine modulation of molecular pathways. These findings with human cells in a clinically relevant model of myocardial ischemia/reperfusion in immunocompetent animals may have significant translational implications.Visual OverviewAn online visual overview is available for this article.