Improved cardiac function in infarcted mice after treatment with pluripotent embryonic stem cells

Timothy J. Nelson, Zhi Dong Ge, Jordan Van Orman, Matthew Barron, Diane Rudy-Reil, Timothy A. Hacker, Ravi Misra, Stephen A. Duncan, John A. Auchamdpach, John W. Lough

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Because pluripotent embryonic stem cells (ESCs) are able to differentiate into any tissue, they are attractive agents for tissue regeneration. Although improvement of cardiac function has been observed after transplantation of pluripotent ESCs, the extent to which these effects reflect ESC-mediated remuscularization, revascularization, or paracrine mechanisms is unknown. Moreover, because ESCs may generate teratomas, the ability to predict the outcome of cellular differentiation, especially when transplanting pluripotent ESCs, is essential; conversely, a requirement to use predifferentiated ESCs would limit their application to highly characterized subsets that are available in limited numbers. In the experiments reported here, we transplanted low numbers of two murine ESC lines, respectively engineered to express a β-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (α-myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC-derived tumors formed within the pericardial space in 21% of injected hearts, lacZ histochemistry revealed that engraftment of ESC was restricted to the ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did not form tumors revealed functional improvements by 4 weeks postinfarction, including significant increases in ejection fraction, circumferential fiber shortening velocity, and peak mitral blood flow velocity. These experiments indicate that the infarcted myocardial environment can support engraftment and cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial functional recovery.

Original languageEnglish (US)
Pages (from-to)1216-1224
Number of pages9
JournalAnatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology
Volume288
Issue number11
DOIs
StatePublished - Nov 1 2006

Keywords

  • Echocardiography
  • Elongation factor promoter
  • Embryonic stem cells
  • LacZ histochemistry
  • Mouse myocardial infarction
  • Myosin heavy chain promoter

ASJC Scopus subject areas

  • Anatomy
  • Agricultural and Biological Sciences (miscellaneous)

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    Nelson, T. J., Ge, Z. D., Van Orman, J., Barron, M., Rudy-Reil, D., Hacker, T. A., Misra, R., Duncan, S. A., Auchamdpach, J. A., & Lough, J. W. (2006). Improved cardiac function in infarcted mice after treatment with pluripotent embryonic stem cells. Anatomical Record - Part A Discoveries in Molecular, Cellular, and Evolutionary Biology, 288(11), 1216-1224. https://doi.org/10.1002/ar.a.20388