Improved cardiac function in infarcted mice after treatment with pluripotent embryonic stem cells. Anat Rec A Discov Mol Cell Evol Biol 2006 Nov;288(11):1216-24
Date
09/28/2006Pubmed ID
17004246Pubmed Central ID
PMC2566533DOI
10.1002/ar.a.20388Scopus ID
2-s2.0-33750532546 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
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 beta-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (alpha-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.
Author List
Nelson TJ, Ge ZD, Van Orman J, Barron M, Rudy-Reil D, Hacker TA, Misra R, Duncan SA, Auchampach JA, Lough JWAuthors
John A. Auchampach PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMatthew R. Barron PhD Research Scientist I in the Surgery department at Medical College of Wisconsin
John W. Lough PhD Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsCardiac Myosins
Cell Differentiation
Cell Line
Cell Proliferation
Cell Survival
Coronary Circulation
Disease Models, Animal
Echocardiography, Doppler
Embryonic Stem Cells
Genes, Reporter
Heart Neoplasms
Lac Operon
Male
Mice
Mice, Inbred C57BL
Myocardial Infarction
Myocardium
Myosin Heavy Chains
Pluripotent Stem Cells
Promoter Regions, Genetic
Regeneration
Staining and Labeling
Stem Cell Transplantation
Ventricular Function, Left
beta-Galactosidase
