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Ann Thorac Surg 1995;60:12-18
© 1995 The Society of Thoracic Surgeons

Cellular Cardiomyoplasty: Myocardial Regeneration With Satellite Cell Implantation

Ray C.-J. Chiu, MD, PhD, Audrius Zibaitis, MD, Race L. Kao, PhD

McGill University, Montreal, Quebec, Canada, and East Tennessee State University, Johnson City, Tennessee

Background. Damaged skeletal muscle is able to regenerate because of the presence of satellite cells, which are undifferentiated myoblasts. In contrast, destruction of cardiac myocytes is associated with an irreversible loss of myocardium and replacement with scar tissue, because it lacks stem cells. We tested the hypothesis that skeletal muscle satellite cells implanted into injured myocardium can differentiate into cardiac muscle fibers and thus repair damaged heart muscle.

Methods. Two series of canine studies were performed. In the first series (n = 26), satellite cells were isolated from skeletal muscle, cultured, and labeled with tritiated thymidine. The cells were implanted into acutely cryoinjured myocardium and the specimens harvested 4 to 18 weeks later. In the second series (n = 20), satellite cells in culture were labeled with lacZ reporter gene, which encodes production of Escherichia coli ß-galactosidase. Four to 6 weeks later, ß-galactosidase activity was studied using X-Gal stain.

Results. New striated muscles were found in the first series of experiments at the site of implantation, within a dense scar created by cryoinjury. These muscles showed histologic evidence of intercalated discs and centrally located nuclei, similar to those seen in cardiac muscle fibers. Tritiated thymidine radioactivity was not identified clearly, presumably due to dilutional effect as the stem cells replicated repeatedly. In the second series, histochemical studies of reporter gene-labeled and implanted satellite cells revealed the presence of ß-galactosidase within the cells at the implant site, which confirmed the survival of implanted cells.

Conclusions. Our data are consistent with the hypothesis of milieu-influenced differentiation of satellite cells into cardiac-like muscle cells. Confirmation of these findings and its functional capabilities could have important clinical implications.




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M. Jain, H. DerSimonian, D. A. Brenner, S. Ngoy, P. Teller, A. S. B. Edge, A. Zawadzka, K. Wetzel, D. B. Sawyer, W. S. Colucci, et al.
Cell Therapy Attenuates Deleterious Ventricular Remodeling and Improves Cardiac Performance After Myocardial Infarction
Circulation, April 10, 2001; 103(14): 1920 - 1927.
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 Ann. Thorac. Surg.Home page
B. Pouzet, J.-T. Vilquin, A. A. Hagege, M. Scorsin, E. Messas, M. Fiszman, K. Schwartz, and P. Menasche
Factors affecting functional outcome after autologous skeletal myoblast transplantation
Ann. Thorac. Surg., March 1, 2001; 71(3): 844 - 851.
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 J. Thorac. Cardiovasc. Surg.Home page
J.-S. Wang, D. Shum-Tim, J. Galipeau, E. Chedrawy, N. Eliopoulos, and R. C.-J. Chiu
Marrow stromal cells for cellular cardiomyoplasty: Feasibility and potential clinical advantages
J. Thorac. Cardiovasc. Surg., November 1, 2000; 120(5): 999 - 1006.
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 Ann. Thorac. Surg.Home page
K.-J. Yoo, R.-K. Li, R. D. Weisel, D. A.G. Mickle, G. Li, and T. M. Yau
Autologous smooth muscle cell transplantation improved heart function in dilated cardiomyopathy
Ann. Thorac. Surg., September 1, 2000; 70(3): 859 - 865.
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 Circ. Res.Home page
C. Ventura and M. Maioli
Opioid Peptide Gene Expression Primes Cardiogenesis in Embryonal Pluripotent Stem Cells
Circ. Res., August 4, 2000; 87(3): 189 - 194.
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 J. Thorac. Cardiovasc. Surg.Home page
M. Scorsin, A. Hagege, J.-T. Vilquin, M. Fiszman, F. Marotte, J.-L. Samuel, L. Rappaport, K. Schwartz, and P. Menasche
COMPARISON OF THE EFFECTS OF FETAL CARDIOMYOCYTE AND SKELETAL MYOBLAST TRANSPLANTATION ON POSTINFARCTION LEFT VENTRICULAR FUNCTION
J. Thorac. Cardiovasc. Surg., June 1, 2000; 119(6): 1169 - 1175.
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H. Reinecke, G. H. MacDonald, S. D. Hauschka, and C. E. Murry
Electromechanical Coupling between Skeletal and Cardiac Muscle: Implications for Infarct Repair
J. Cell Biol., May 1, 2000; 149(3): 731 - 740.
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 J. Thorac. Cardiovasc. Surg.Home page
R.-K. Li, R. D. Weisel, D. A. G. Mickle, Z.-Q. Jia, E.-J. Kim, T. Sakai, S. Tomita, L. Schwartz, M. Iwanochko, M. Husain, et al.
AUTOLOGOUS PORCINE HEART CELL TRANSPLANTATION IMPROVED HEART FUNCTION AFTER A MYOCARDIAL INFARCTION
J. Thorac. Cardiovasc. Surg., January 1, 2000; 119(1): 62 - 68.
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 Ann. Thorac. Surg.Home page
T. Sakai, R.-K. Li, R. D. Weisel, D. A.G. Mickle, E.-J. Kim, S. Tomita, Z.-Q. Jia, and T. M. Yau
Autologous heart cell transplantation improves cardiac function after myocardial injury
Ann. Thorac. Surg., December 1, 1999; 68(6): 2074 - 2080.
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 CirculationHome page
S. Tomita, R.-K. Li, R. D. Weisel, D. A. G. Mickle, E.-J. Kim, T. Sakai, and Z.-Q. Jia
Autologous Transplantation of Bone Marrow Cells Improves Damaged Heart Function
Circulation, November 9, 1999; 100 (2009): II-247 - II-256.
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 Ann. Thorac. Surg.Home page
B. Z. Atkins, C. W. Lewis, W. E. Kraus, K. A. Hutcheson, D. D. Glower, and D. A. Taylor
Intracardiac transplantation of skeletal myoblasts yields two populations of striated cells in situ
Ann. Thorac. Surg., January 1, 1999; 67(1): 124 - 129.
[Abstract] [Full Text] [PDF]

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 Ann. Thorac. Surg.Home page
R. C.-J. Chiu

Ann. Thorac. Surg., January 1, 1999; 67(1): 129 - 129.
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 Am. J. Physiol. Heart Circ. Physiol.Home page
C. W. Lewis, B. Z. Atkins, K. A. Hutcheson, C. T. Gillen, M. C. Reedy, D. D. Glower, and D. A. Taylor
A load-independent in vivo model for evaluating therapeutic interventions in injured myocardium
Am J Physiol Heart Circ Physiol, November 1, 1998; 275(5): H1834 - H1844.
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 Cardiovasc ResHome page
J. Leor, H. Prentice, V. Sartorelli, M. J Quinones, M. Patterson, L. K Kedes, and R. A Kloner
Gene transfer and cell transplant: an experimental approach to repair a 'broken heart'
Cardiovasc Res, September 1, 1997; 35(3): 431 - 441.
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 Ann. Thorac. Surg.Home page
I. Y. Christlieb, R. C.-J. Chiu, A. Zibaitis, and R. L. Kao
Cellular Cardiomyoplasty
Ann. Thorac. Surg., February 1, 1996; 61 (2): 772 - 773.
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 J. Thorac. Cardiovasc. Surg.Home page
R. E. Oakley, N. J. Brand, P. B. Burton, M. C. McMullen, G. B. Adams, M. C. Poznansky, P. J. Barton, and M. H. Yacoub
Efficiency of a high-titer retroviral vector for gene transfer into skeletal myoblasts
J. Thorac. Cardiovasc. Surg., January 1, 1994; 115(1): 1 - 8.
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 J. Biol. Chem.Home page
M. L. Whitney, K. G. Otto, C. A. Blau, H. Reinecke, and C. E. Murry
Control of Myoblast Proliferation with a Synthetic Ligand
J. Biol. Chem., October 26, 2001; 276(44): 41191 - 41196.
[Abstract] [Full Text] [PDF]


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