Functional consequences of human induced pluripotent stem cell therapy: Myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling

Qiang Xiong, Lei Ye, Pengyuan Zhang, Michael Lepley, Jinfeng Tian, Jun Li, Liying Zhang, Cory Swingen, J. Thomas Vaughan, Dan S. Kaufman, Jianyi Zhang

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

Background-: The use of cells derived from human induced pluripotent stem cells as cellular therapy for myocardial injury has yet to be examined in a large-animal model. Methods and Results-: Immunosuppressed Yorkshire pigs were assigned to 1 of 3 groups: A myocardial infarction group (MI group; distal left anterior descending coronary artery ligation and reperfusion; n=13); a cell-treatment group (MI with 4×10 vascular cells derived from human induced pluripotent stem cells administered via a fibrin patch; n=14); and a normal group (n=15). At 4 weeks, left ventricular structural and functional abnormalities were less pronounced in hearts in the cell-treated group than in MI hearts (P<0.05), and these improvements were accompanied by declines in scar size (10.4±1.6% versus 8.3±1.1%, MI versus cell-treatment group, P<0.05). The cell-treated group displayed a significant increase in vascular density and blood flow (0.83±0.11 and 1.05±0.13 mL·min·g, MI versus cell-treatment group, P<0.05) in the periscar border zone (BZ), which was accompanied by improvements in systolic thickening fractions (infarct zone,-10±7% versus 5±5%; BZ, 7±4% versus 23±6%; P<0.05). Transplantation of vascular cells derived from human induced pluripotent stem cells stimulated c-kit cell recruitment to BZ and the rate of bromodeoxyuridine incorporation in both c-kit cells and cardiomyocytes (P<0.05). Using a magnetic resonance spectroscopic saturation transfer technique, we found that the rate of ATP hydrolysis in BZ of MI hearts was severely reduced, and the severity of this reduction was linearly related to the severity of the elevations of wall stresses (r=0.82, P<0.05). This decline in BZ ATP utilization was markedly attenuated in the cell-treatment group. Conclusions-: Transplantation of vascular cells derived from human induced pluripotent stem cells mobilized endogenous progenitor cells into the BZ, attenuated regional wall stress, stimulated neovascularization, and improved BZ perfusion, which in turn resulted in marked increases in BZ contractile function and ATP turnover rate.

Original languageEnglish (US)
Pages (from-to)997-1008
Number of pages12
JournalCirculation
Volume127
Issue number9
DOIs
StatePublished - Mar 5 2013

Keywords

  • adenosine triphosphate
  • heart
  • hypertrophy
  • myocardium
  • stem cells

Fingerprint Dive into the research topics of 'Functional consequences of human induced pluripotent stem cell therapy: Myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling'. Together they form a unique fingerprint.

  • Cite this

    Xiong, Q., Ye, L., Zhang, P., Lepley, M., Tian, J., Li, J., Zhang, L., Swingen, C., Vaughan, J. T., Kaufman, D. S., & Zhang, J. (2013). Functional consequences of human induced pluripotent stem cell therapy: Myocardial ATP turnover rate in the in vivo swine heart with postinfarction remodeling. Circulation, 127(9), 997-1008. https://doi.org/10.1161/CIRCULATIONAHA.112.000641