Skip to main content
SpringerLink
Log in

Myoblast-Based Cell Transplantation

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

Cell transplantation is emerging as a new treatment designed tot improve the poor outcome of patients with cardiac failure. Its rationale is that implantation of contractile cells into postinfarction scars can functionally rejuvenate these areas. Primarily for practical reasons, autologous skeletal myoblasts have been the first to be tested clinically but bone marrow stromal and hematopoietic stem cells may represent an interesting alternative in select situations because of their autologous origin and their purported plasticity. However, several key issues still need to be addressed including (1) the optimal type of cells, (2) the mechanism by which cell engraftment improves cardiac function, i.e., increased contractility or limitation of remodeling, (3) the most effective strategies for optimizing cell survival, and (4) the potential benefits of cell transplantation in nonischemic heart failure. In parallel to the experimental studies designed to address these issues, initial clinical trials are underway and should hopefully allow to know whether the hopes raised by cellular therapy are met by clinically meaningful improvements in function and outcome in patients with severe left ventricular ischemic dysfunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Stewart S, Jenkins A, Buchan S, McGuire A, Capewell S, McMurray JJJV. The current cost of heart failure to the National Helth Service in the UK. Eur J Heart Failure 2002;4:361-371.

    Google Scholar 

  2. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA. Myocyte proliferation in end-stage cardiac failure in humans. Proc Natl Acad Sci USA 1998;95:8801-8805.

    PubMed  Google Scholar 

  3. Beltrami AP, Urbanek K, Kajstura J, et al. Evidence that human cardiac myocytes divide after myocardial infarction. N Engl J Med 2001;344:1750-1757.

    PubMed  Google Scholar 

  4. Tam SKC, Gu W, Nadal-Ginard B, Vlahakes GJ. Molecular cardiomyoplasty: Potential cardiac gene therapy for chronic heart failure. J Thorac Cardiovasc Surg 1995;109:918-924.

    PubMed  Google Scholar 

  5. Yoo KJ, Li RK, Weisel RD, et al. Heart cell transplantation improves heart function in dilated cardiomyopathic hamsters. Circulation 2000;102(Suppl III):III-204-209.

    Google Scholar 

  6. Scorsin M, Hagège AA, Dolizy I, Marotte F, Mirochnik N, Copin H, et al. Can cellular transplantation improve function in doxorubicin-induced heart failure? Circulation 1998;98(Suppl II):II-151-156.

    Google Scholar 

  7. Hutcheson KA, Atkins BZ, Hueman MT, Hopkins MB, Glower DD, Taylor DA. Comparison of benefits on myocardial performance of cellular cardiomyoplasty with skeletal myoblasts and fibroblasts. Cell Transplant 2000;9:359-368.

    PubMed  Google Scholar 

  8. Li RK, Jia Z-Q, Weisel RD, Merante F, Mickle DAG. Smooth muscle cell transplantation into myocardial scar tissue improves heart function. J Mol Cell Cardiol 1999;31:513-522.

    PubMed  Google Scholar 

  9. Leor J, Patterson M, Quinones MJ, Kedes LH, Kloner RA. Transplantation of fetal myocardial tissue into the infarcted myocardium of rat. Circulation 1996;94(Suppl II):II-332-336.

    Google Scholar 

  10. Scorsin M, Hagège AA, Marotte F, et al. Does transplantation of cardiomyocytes improve function of infarcted myocardium. Circulation 1997;96(Suppl II):II-188-193.

    Google Scholar 

  11. Li R-K, Jia Z-Q, Weisel RD, et al. Cardiomyocyte transplantation improves heart function. Ann Thorac Surg 1996;62:654-661.

    PubMed  Google Scholar 

  12. Ghostine S, Carrion C, Guarita Sousa LC, et al. Long-term efficacy of myoblast transplantation on regional structure and function after myocardial infarction. Circulation 2002;106(Suppl I):I-131-136.

    Google Scholar 

  13. Murry CE, Wiseman RW, Schwartz SM, Hauschka SD. Skeletal myoblast transplantation for repair of myocardial necrosis. J Clin Invest 1996;98:2512-2523.

    PubMed  Google Scholar 

  14. Reinecke H, MacDonald GH, Hauschka SD, Murry CE. Electromechanical coupling between skeletal and cardiac muscle: Implications for infarct repair. J Cell Biol 2000;149:731-740.

    PubMed  Google Scholar 

  15. Kao RL, Chin TK, Ganote CE, Hossler FE, Li C, Browder W. Satellite cell transplantation to repair injured myocardium. CVR 2000;1:31-42.

    Google Scholar 

  16. Taylor DA, Atkins BZ, Hungspreugs P, et al. Regenerating functional myocardium: Improved performance Myoblast Transplantation 227 after skeletal myoblast transplantation. Nature Medicine 1998;4:929-933.

    PubMed  Google Scholar 

  17. Rajnoch C, Chachques J-C, Berrebi A, Bruneval P, Benoit M-O, Carpentier A. Cellular therapy reverses myocardial dysfunction. J Thorac Cardiovasc Surg 2001;121:871-878.

    PubMed  Google Scholar 

  18. Jain M, DerSimonian H, Brenner DA, et al. Cell therapy attenuates deleterious ventricular remodeling and improves cardiac performance after myocardial infarction. Circulation 2001;103:1920-1927.

    PubMed  Google Scholar 

  19. Pouzet B, Ghostine S, Vilquin JT, et al. Is skeletal myoblast transplantation clinically relevant in the era of angiotensin-converting enzyme inhibitors? Circulation 2001;104(Suppl I):I-223-228.

    Google Scholar 

  20. Pouzet B, Ghostine S, Alattar N, et al. Long term functional results of autologous skeletal myoblast transplantation in rats. Circulation 2001;104(Suppl II):599 (abstract).

    Google Scholar 

  21. Pouzet B, Vilquin J-T, Hagège AA, et al. Factors affecting functional outcome after autologous skeletal myoblast transplantation. Ann Thorac Surg 2001;71:844-851.

    PubMed  Google Scholar 

  22. Zhang M, Methot D, Poppa V, Fujio Y, Walsh K, Murry CE. Cardiomyocyte grafting for cardiac repair: Graft cell death and anti-death strategies. J Mol Cell Cardiol 2001;33:907-921.

    PubMed  Google Scholar 

  23. Sakakibara Y, Tambara K, Lu F, et al. Cardiomyocyte transplantation does not reverse cardiac remodeling in rats with chronic myocardial infarction. Ann Thorac Surg 2002;74:25-30.

    PubMed  Google Scholar 

  24. Nakamura T, Mizuno S, Matsumoto K, Sawa Y, Matsuda H, Nakamura T. Myocardial protection from ischemia/reperfusion injury by endogenous and exogenous HGF. J Clin Invest 2000;106:1511-1519.

    PubMed  Google Scholar 

  25. Ueda H, Sawa Y, Matsumoto K, et al. Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart. Ann Thorac Surg 1999;67:1726-1731.

    PubMed  Google Scholar 

  26. Taniyama Y, Morishita R, Nagakami H, et al. Potential contribution of a novel antifibrotic factor, hepatocyte growth factor, to prevention of myocardial fibrosis by angiotensin II blockade in cardiomyopathic hamsters. Circulation 2000;102:246-252.

    PubMed  Google Scholar 

  27. Miyagawa S, Sawa Y, Taketani S, et al. Myocardial regeneration therapy for heart failure. Hepatocyte growth factor enhances the effects of cellular cardiomyoplasty. Circulation 2002;105:2556-2561.

    PubMed  Google Scholar 

  28. Anversa P, Nadal-Ginard B. Myocyte renewal and ventricular remodelling. Nature 2002;415:240-243.

    PubMed  Google Scholar 

  29. Scorsin M, Hagège AA, Vilquin J-T, et al. Comparison of the effects of fetal cardiomyocytes and skeletal myoblast transplantation on postinfarction left ventricular function. J Thorac Cardiovasc Surg 2000;119:1169-1175.

    PubMed  Google Scholar 

  30. Menasché P, Hagège AA, Scorsin M, et al. Myoblast transplantation for heart failure. Lancet 2001;357:279-280.

    PubMed  Google Scholar 

  31. Menasché P, Hagège A, Vilquin J-T, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol 2003;41:1078-1083.

    PubMed  Google Scholar 

  32. Moss AJ, Zareba W, Hall J, et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. New Engl J Med 2002;346:877-883.

    PubMed  Google Scholar 

  33. Pagani F, Dersimonian R, Zawadska A, et al. Autologous skeletal myoblasts transplanted to ischemia damaged myocardium in humans. J Am Coll Cardiol 2003;41:879-888.

    PubMed  Google Scholar 

  34. Grossman PM, Han Z, Palasis M, Barry JJ, Lederman RJ. Incomplete retention after direct myocardial injection. Cathet Cardovasc Intervent 2002;55:392-397.

    Google Scholar 

  35. Thomson CA, Nasseri BA, Makower J, et al. Percutaneous transvenous cellular cardiomyoplasty: A novel nonsurgical approach for myocardial cell transplantation. J Am Coll Cardiol 2002;39(Suppl A) 75A (abstract).

    Google Scholar 

  36. Beauchamp JR, Morgan JE, Pagel CN, Partridge TA. Dynamics of myoblast transplantation reveal a discrete minority of precursors with stem cell-like properties as the myogenic source. J Cell Biol 1999;144:1113-1121.

    PubMed  Google Scholar 

  37. Karasuno T. Autologous graft-versus-host disease. Int J Hematol 1997;65:105-113.

    PubMed  Google Scholar 

  38. Skuk D, Tremblay JP. Complement deposition and cell death after myoblast transplantation. Cell Transplant 1998;7:427-434.

    PubMed  Google Scholar 

  39. Suzuki K, Murtuza B, Smolenski RT, et al. Cell transplantation for the treatment of acute myocardial infarction using vascular endothelial growth factor-expressing skeletal myoblasts. Circulation 2001;104(Suppl I):I-207-212.

    Google Scholar 

  40. Sakakibara Y, Nishimura K, Tambara K, et al. Prevascularization with gelatin microspheres containing basic fibroblast growth factor enhances the benefits of cardiomyocyte transplantation. J Thorac Cardiovasc Surg 2002;124:50-56.

    PubMed  Google Scholar 

  41. Suzuki K, Smolenski RT, Jayakumar J, Murtuza B, Brand NJ, Yacoub MH. Heat shock treatment enhances graft cell survival in skeletal myoblast transplantation to the heart. Circulation 2000;102(Suppl III):III-216-221.

    Google Scholar 

  42. Li RK, Mickle DAG, Weisel RD, Rao V, Jia ZQ. Optimal time for cardiomyocyte transplantation to maximize myocardial function after left ventricular injury. Ann Thorac Surg 2001;72:1957-1963.

    PubMed  Google Scholar 

  43. Edom-Vovard F, Mouly V, Barbet JP, Butler-Browne GS. The four populations of myoblasts involved in human limb muscle formation are present from the onset of primary myotube formation. J Cell Sci 1999;112(Pt2):191-199.

    PubMed  Google Scholar 

  44. Suzuki K, Brand NJ, Khan MA, et al. Overexpression of connexin 43 in skeletal myoblasts: Relevance to cell transplantation to the heart. J Thoracic Cardiovasc Surg 2001;122:759-766.

    Google Scholar 

  45. Strauer BE, Brehm M, Zeus T, et al. repair of infracted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 2002;106:1913-1918.

    PubMed  Google Scholar 

  46. Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA 2001;98:10344-10349.

    PubMed  Google Scholar 

  47. Kocher AA, Schuster MD, Szabolcs MJ, et al. Neovascularization of ischemic myocardium by human bone-marrowderived angioblasts prevents cardiomyocyte apoptosis, reduces remodeling and improves cardiac function. Nature Medicine 2001;4:430-436.

    Google Scholar 

  48. Condorelli G, Borello U, De Angelis L, et al. Cardiomyocyte induce endothelial cells to trans-differentiate into cardiac muscle: Implications for myocardium regeneration. Proc Natl Acad Sci USA 2001;98:10733-10738.

    PubMed  Google Scholar 

  49. Saito T, Kuang JQ, Bittira B, Al-Khaldi A, Chiu RCJ. Xenotransplant cardiac chimera: Immune tolerance of adult stem cells. Ann Thorac Surg 2002;74:19-24.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Cardiovascular Surgery, Hôpital Européen Georges Pompidou, Paris, France

    Philippe Menasché

Authors
  1. Philippe Menasché
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Menasché, P. Myoblast-Based Cell Transplantation. Heart Fail Rev 8, 221–227 (2003). https://doi.org/10.1023/A:1024705214292

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1024705214292

Search

Navigation