Journal of the Chinese Medical Association
Volume 71, Issue 2 , Pages 79-85, February 2008

Cardiac Myocyte Progenitors from Adult Hearts for Myocardial Regenerative Therapy

  • Chia-Feng Yang

      Affiliations

    • Department of Pediatrics, and Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • ,
  • Kuang-Yi Chou

      Affiliations

    • National Taipei College of Nursing, and National Yang-Ming University, Taipei, Taiwan, R.O.C.
    • ,
  • Zen-Chung Weng

      Affiliations

    • Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • School of Medicine and Taipei, Taiwan, R.O.C.
    • ,
  • Shih-Chieh Hung

      Affiliations

    • Institute of Clinical Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Shiau-Ting Lai

      Affiliations

    • Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • School of Medicine and Taipei, Taiwan, R.O.C.
    • ,
  • Chiao-Po Hsu

      Affiliations

    • Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • Institute of Clinical Medicine, Taipei, Taiwan, R.O.C.
    • ,
  • Jih-Shiuan Wang

      Affiliations

    • Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C.
    • School of Medicine and Taipei, Taiwan, R.O.C.
    • Corresponding Author InformationCorrespondence to: Dr Jih-Shiuan Wang, Division of Cardiovascular Surgery, Department of Surgery, Taipei Veterans General Hospital, 201, Section 2, Shih-Pai Road, Taipei 112, Taiwan, R.O.C

Received 24 July 2006; accepted 3 January 2007.

Article Outline

Background

The heart is a highly vascular organ and prolonged interruption of myocardial blood flow initiates events that culminate in cardiac myocyte death. Proposed experimental reparative strategies include harvesting potent cells followed by direct injection into ischemic myocardium to achieve myogenesis and angiogenesis.

Methods

Accordingly, we set out to isolate and expand a purified population of adult rat putative cardiomyocyte precursors, and to identify their characteristics in vitro. By using an acute myocardial infarction model and direct cell implantation, we further tested the hypothesis that these cells are an ideal cell source for myocardial regeneration and can enhance cardiac repair after implantation into the ischemic rat heart.

Results

We describe here the identification of a subpopulation of primitive cells from rat heart, processing stem cell marker, c-kit and myogenic transcriptional factors, GATA-4 and MEF 2C, and cardiac specific proteins, troponin-I, a-sarcomeric actinin and connexin-43. They exhibited a high in vitro proliferative potential. These findings strongly suggest that these cells are putative cardiomyocyte precursors. After transplantation, they were able to be retained and proliferate (13.63 ± 5.97% after 2 weeks) within the ischemic heart. Progeny of implanted cells migrated along the infarcted scar, reconstituted regenerated cardiomyocytes with incorporation into host myocardium, and inhibited cardiac remodeling with decreased scar formation.

Conclusion

Our findings suggest that putative cardiomyocyte precursors isolated from adult heart could potentially be an autologous cell source for myocardial regeneration cell therapy.

Key Words:  cells , myocytes , myocardial infarction

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References 

  1. Williams RS , Benjamin IJ . Protective responses in the ischemic myocardium . J Clin Invest . 2000;106:813–818
  2. Wang JS , Shum-Tim D , Galipeau J , Chedrawy E , Eliopoulos N , Chiu RC . Marrow stromal cells for cellular cardiomyoplasty: feasibility and potential clinical advantages . J Thorac Cardiovasc Surg . 2000;120:999–1005
  3. Orlic D , Kajstura J , Chimenti S , Bodine DM , Leri A , Anversa P . Bone marrow cells regenerate infarcted myocardium . Ped Transplant . 2003;7:86–88
  4. Jackson KA, Majka SM, Wang H, Pocius J, Hartley CJ, Majesky MW, et al  Regeneration of ischemic cardiac muscle and vascular endothelium by adult stem cells . J Clin Invest . 2001;107:1395–1402
  5. Reinecke H , Zhang M , Bartosek T , Murry CE . Survival, integration, and differentiation of cardiomyocyte grafts: a study in normal and injured rat hearts . Circulation . 1999;100:193–202
  6. 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
  7. McDevitt TC , Woodhouse KA , Hauschka SD , Murry CE , Stayton PS . Spatially organized layers of cardiomyocytes on biodegradable polyurethane films for myocardial repair . J Biomed Mater Res . 2003;66:586–595
  8. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al  Adult cardiac stem cells are multipotent and support myocardial regeneration . Cell . 2003;114:763–776
  9. Anversa P , Nadal-Ginard B . Myocyte renewal and ventricular remodeling . Nature . 2002;415:240–243
  10. Tam SK , Gu W , Mahdavi V , Nadal-Ginard B . Cardiac myocyte terminal differentiation. Potential for cardiac regeneration . Ann NY Acad Sci . 1995;752:72–79
  11. Beltrami AP, Urbanek K, Kajstura J, Yan SM, Finato N, Bussani R, et al  Evidence that human cardiac myocytes divide after myocardial infarction . N Engl J Med . 2001;344:1750–1757
  12. Quaini F, Urbanek K, Beltrami AP, Finato N, Beltrami CA, Nadal-Ginard B, et al  Chimerism of the transplanted heart . N Engl J Med . 2002;346:1410–1412
  13. Urbanek K, Quaini F, Tasca G, Torella D, Castaldo C, Nadal-Ginard B, et al  Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy . Proc Natl Acad Sci USA . 2003;100:10440–10445
  14. Mangi AA, Noiseux N, Kong D, He H, Rezvani M, Ingwall JS, et al. Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts . Nat Med . 2003;9:1195–1201

PII: S1726-4901(08)70079-0

doi:10.1016/S1726-4901(08)70079-0

Journal of the Chinese Medical Association
Volume 71, Issue 2 , Pages 79-85, February 2008

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