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

Authors

  • Timothy J. Nelson,

    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Zhi-Dong Ge,

    1. Department of Pharmacology and Toxicology and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Jordan Van Orman,

    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Matthew Barron,

    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Diane Rudy-Reil,

    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Timothy A. Hacker,

    1. Department of Medicine, Section of Cardiovascular Medicine, University of Wisconsin, Madison, Wisconsin
    Search for more papers by this author
  • Ravi Misra,

    1. Department of Biochemistry and the Cardiovascular Center Medical Collegeof Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • Stephen A. Duncan,

    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • John A. Auchampach,

    1. Department of Pharmacology and Toxicology and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    Search for more papers by this author
  • John W. Lough

    Corresponding author
    1. Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center Medical College of Wisconsin, Milwaukee, Wisconsin
    • Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226
    Search for more papers by this author
    • Fax: 414-456-6517


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. Anat Rec Part A, 288A:1216–1224, 2006. © 2006 Wiley-Liss, Inc.

Ancillary