Transplantation of Human Umbilical Cord Blood-Derived Cellular Fraction Improves LV Function and Remodeling after Myocardial Ischemia/Reperfusion

• Published in: Circulation research
• Main Authors: Zhao, Lin, Cheng, Guangming, Choksi, Kashyap, Samanta, Anweshan, Girgis, Magdy, Soder, Rupal P, Vincent, Robert J, Wulser, Michael, De Ruyter, Matthew, McEnulty, Patrick, Hauptman, Jeryl, Yang, Yanjuan, Weiner, Carl P, Dawn, Buddhadeb
• Format: Journal Article
• Language: English
• Published: United States 29.08.2019
• Subjects: cardiac repair; umbilical cord blood; nonhematopoietic
• ISSN: 1524-4571

Human umbilical cord blood (hUCB) contains diverse populations of stem/progenitor cells. Whether hUCB-derived nonhematopoietic cells would induce cardiac repair remains unknown. To examine whether intramyocardial transplantation of hUCB-derived CD45 Lin nonhematopoietic cellular fraction after a reperfused myocardial infarction in nonimmunosuppressed rats would improve cardiac function and ameliorate ventricular remodeling. Nonhematopoietic CD45 Lin cells were isolated from hUCB. Flow cytometry and qPCR were used to characterize this subpopulation. Age-matched male Fischer 344 rats underwent a 30-min coronary occlusion followed by reperfusion, and 48 h later received intramyocardial injection of vehicle or hUCB CD45 Lin cells. After 35 d, compared with vehicle-treated rats, CD45 Lin cell-treated rats exhibited improved left ventricular (LV) function, blunted LV hypertrophy, greater preservation of viable myocardium in the infarct zone, and superior LV remodeling. Mechanistically, hUCB CD45 Lin 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 d after MI. Transplantation of hUCB-derived CD45 Lin nonhematopoietic cellular subfraction after a reperfused MI in nonimmunosuppressed rats ameliorates LV 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.