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Experimental models for cardiac regeneration

Nature Clinical Practice Cardiovascular Medicine volume 3, pages S29–S32 (2006)Cite this article

Abstract

Simple ex vivo or in vitro models are most useful for testing putative cell therapy protocols, as they allow quick and controlled screening of variants and possible improvements. We discuss here three different models: coculture of precursors of human bone marrow cells (BMCs) with mouse heart slices bearing a cryogenic lesion; coculture of human BMCs and rat cardiomyocytes separated by a porous membrane that allows passage of soluble substances but prevents migration of nuclear material; and injection of human BMCs in developing chick heart bearing burn lesions. Our results indicate that the damaged areas express specific genes such as MPC1 and SDF1, and that some human BMCs migrate and graft near the lesion, where they can originate cells with a cardiac phenotype that produce human cardiac proteins. The frequency of this transformation is, however, very low. Understanding the factors that determine and regulate nuclear reprogramming and transdifferentiation would be crucial to appraising the contribution of these phenomena to cardiac regeneration and, eventually, to modulating them with therapeutic intent.

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Figure 1: Coculture with rat cardiomyocytes induces expression of human myosin heavy chain in human mononuclear bone marrow cells
Figure 2: Homing of human mononuclear cells in the chick embryo heart

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References

  1. Anversa P and Nadal-Ginard B (2002) Myocyte renewal and ventricular remodelling. Nature 415: 240–243

    Article  CAS  Google Scholar 

  2. Orlic D et al. (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410: 701–705

    Article  CAS  Google Scholar 

  3. Kajstura J et al. (2005) Bone marrow cells differentiate in cardiac cell lineages after infarction independently of cell fusion. Circ Res. 96: 127–137

    Article  CAS  Google Scholar 

  4. Strauer BE et al. (200) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106: 1913–1918

  5. Assmus B et al. (2002) Transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction (TOPCARE-AMI). Circulation 106: 3009–3017

    Article  Google Scholar 

  6. Stamm C et al. (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361: 45–46

    Article  Google Scholar 

  7. Saito T et al. (2003) Transcoronary implantation of bone marrow stromal cells ameliorates cardiac function after myocardial infarction. J Thorac Cardiovasc Surg 126: 114–123

    Article  Google Scholar 

  8. Badorff C et al. (2003) Transdifferentiation of blood-derived human adult endothelial progenitor cells into functionally active cardiomyocytes. Circulation 107: 1024–1032

    Article  Google Scholar 

  9. Tse HF et al. (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361: 47–49

    Article  Google Scholar 

  10. Perin EC et al. (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107: 2294–2302

    Article  Google Scholar 

  11. Fuchs S et al. (2003) Catheter-based autologous bone marrow myocardial injection in no-option patients with advanced coronary artery disease: a feasibility study. J Am Coll Cardiol 41: 1721–1724

    Article  Google Scholar 

  12. Fernández-Avilés F et al. (2004) Experimental and clinical regenerative capability of human bone marrow cells after myocardial infarction. Circ Res 95: 742–748

    Article  Google Scholar 

  13. Wollert KC et al. (2004) Intracoronary autologous bone marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet 364: 141–148

    Article  Google Scholar 

  14. Lange C et al. (2005) High-potential human mesenchymal stem cells. Stem Cells Dev 14: 70–80

    Article  CAS  Google Scholar 

  15. Herzog EL et al. (2003) Plasticity of marrow-derived stem cells. Blood 102: 3483–3493

    Article  CAS  Google Scholar 

  16. Zuk PA et al. (2002) Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell 13: 4279–4295

    Article  CAS  Google Scholar 

  17. Thomas SP et al. (2000) Synthetic strands of neonatal mouse cardiac myocytes: structural and electrophysiological properties. Circ Res 87: 467–473

    Article  CAS  Google Scholar 

  18. Kehat I et al. (2001) Human embryonic stem cells can differentiate into myocytes with structural and functional properties of cardiomyocytes. J Clin Invest 108: 407–414

    Article  CAS  Google Scholar 

  19. Abbott JD et al. (2004) Stromal cell-derived factor-1alpha plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury. Circulation 110: 3300–3305

    Article  Google Scholar 

  20. Ma J et al. (2005) Time course of myocardial stromal cell-derived factor 1 expression and beneficial effects of intravenously administered bone marrow stem cells in rats with experimental myocardial infarction. Basic Res Cardiol 100: 217–223

    Article  CAS  Google Scholar 

  21. Limbourg FP, Drexler H. (2005) Bone marrow cells for myocardial infarction. Effect or mediator? Circ Res 96: 6–8

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Support from Fondo de Investigaciones Sanitarias de la Seguridad Social, grant PI-041486, Fundación de Investigación Médica de la Mutua Madrileña and Red de Terapia Celular del Instituto de Salud Carlos III is gratefully acknowledged.

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Authors and Affiliations

  1. Associated Professor of Physiology, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain

    Ana Sánchez

  2. Postdoctoral Research Fellows, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain

    María Eugenia Fernández & Arancha Rodríguez

  3. Senior Technician, Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain

    Jesús Fernández

  4. Professor of Physiology at the Instituto de Biología y Genética Molecular (IBGM), Facultad de Medicina, Universidad de Valladolid, Valladolid, Spain

    Javier García-Sancho

  5. a Doctoral Student Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain

    Nuria Torre-Pérez

  6. Professor of Anatomy at the Departamento de Anatomía y Biología Celular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain

    Juan M Hurlé

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  1. Ana Sánchez
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  2. María Eugenia Fernández
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  4. Jesús Fernández
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  7. Javier García-Sancho
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Correspondence to Ana Sánchez.

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Sánchez, A., Fernández, M., Rodríguez, A. et al. Experimental models for cardiac regeneration. Nat Rev Cardiol 3 (Suppl 1), S29–S32 (2006). https://doi.org/10.1038/ncpcardio0458

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