Cellular cardiomyoplasty improves survival after myocardial injury.
BACKGROUND
Cellular cardiomyoplasty is discussed as an alternative therapeutic approach to heart failure. To date, however, the functional characteristics of the transplanted cells, their contribution to heart function, and most importantly, the potential therapeutic benefit of this treatment remain unclear.


RESULTS
Murine ventricular cardiomyocytes (E12.5-E15.5) labeled with enhanced green fluorescent protein (EGFP) were transplanted into the cryoinjured left ventricular walls of 2-month-old male mice. Ultrastructural analysis of the cryoinfarction showed a complete loss of cardiomyocytes within 2 days and fibrotic healing within 7 days after injury. Two weeks after operation, EGFP-positive cardiomyocytes were engrafted throughout the wall of the lesioned myocardium. Morphological studies showed differentiation and formation of intercellular contacts. Furthermore, electrophysiological experiments on isolated EGFP-positive cardiomyocytes showed time-dependent differentiation with postnatal ventricular action potentials and intact beta-adrenergic modulation. These findings were corroborated by Western blotting, in which accelerated differentiation of the transplanted cells was detected on the basis of a switch in troponin I isoforms. When contractility was tested in muscle strips and heart function was assessed by use of echocardiography, a significant improvement of force generation and heart function was seen. These findings were supported by a clear improvement of survival of mice in the cardiomyoplasty group when a large group of animals was analyzed (n=153).


CONCLUSIONS
Transplanted embryonic cardiomyocytes engraft and display accelerated differentiation and intact cellular excitability. The present study demonstrates, as a proof of principle, that cellular cardiomyoplasty improves heart function and increases survival on myocardial injury.
Roell
Wilhelm
W
Department of Cardiac Surgery, University of Bonn, Bonn, Germany.
Lu
Zhong J
ZJ
Bloch
Wilhelm
W
Siedner
Sharon
S
Tiemann
Klaus
K
Xia
Ying
Y
Stoecker
Eva
E
Fleischmann
Michaela
M
Bohlen
Heribert
H
Stehle
Robert
R
Kolossov
Eugen
E
Brem
Gottfried
G
Addicks
Klaus
K
Pfitzer
Gabriele
G
Welz
Armin
A
Hescheler
Juergen
J
Fleischmann
Bernd K
BK
D000818:Animals; D015153:Blotting, Western; D018421:Cardiomyoplasty / Q000379:methods*; D002454:Cell Differentiation; D002470:Cell Survival; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D004452:Echocardiography; D004594:Electrophysiology; D016332:Fetal Tissue Transplantation; D017930:Genes, Reporter; D006085:Graft Survival; D006334:Heart Function Tests; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D015996:Survival Rate; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000628:therapy