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  • Review Article
  • Published:

Cell therapy for the treatment of coronary heart disease: a critical appraisal

Nature Reviews Cardiology volume 7, pages 204–215 (2010)Cite this article

Subjects

Abstract

Randomized, controlled clinical trials have demonstrated that cell therapy can improve the recovery of cardiac function in patients after acute myocardial infarction (AMI). Trial results are inconsistent, however, and uncertainty persists regarding the mechanism of action and prospect of cell therapy for patients with heart disease. This Review examines the results from the first-generation trials and discusses procedure-related variables that could have determined treatment outcomes. Obvious issues, including optimal timing of cell transfer, dose, and delivery methods are being investigated in ongoing second-generation trials. These studies aim to refine the protocols and identify the patients who will benefit most from cell therapy. Third-generation trials will address the current limitations of cell therapy, such as cell retention and cell survival after transplantation, and impaired cell functionality in patients with advanced cardiovascular disease. The secretion of factors with paracrine effects by the transplanted cells is an increasingly recognized phenomenon. Identification of these factors, by secretome analyses and bioinformatic approaches, could advance protein-based therapies to promote healing and inhibit pathological remodeling of the heart after AMI. The identification of reliable sources of pluripotent stem cells and their differentiation into mature cardiac cell types could ultimately enable regeneration of the infarcted heart.

Key Points

  • Clinical trials show that bone marrow cell therapy improves myocardial perfusion and contractile performance in patients with acute myocardial infarction, heart failure, and chronic myocardial ischemia

  • Trial results are not uniform, however, probably owing to the current lack of standardization and optimization of cell isolation and delivery protocols

  • Ongoing clinical trials are addressing these limitations in an attempt to develop robust and reproducible cell therapy protocols that can be applied more widely and improve clinical outcome

  • Bone marrow cells are thought to have paracrine effects on neovascularization, inflammation, wound healing and possibly resident stem and progenitor cells

  • Secretome analyses could lead to the identification of paracrine factors with therapeutic potential for patients with coronary heart disease

  • Pluripotent stem cells provide an opportunity to generate patient-specific cardiac cells, but tumorgenicity and poor engraftment after transplantation currently limit their use for regenerative cell therapy and tissue engineering

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Figure 1: Secretome analyses to identify new cardioactive paracrine factors.
Figure 2: Sources of cardiac progenitor cells.

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Acknowledgements

We thank Dr. Kerstin Bethmann for assistance with the tables and figures. This work was supported by the Deutsche Forschungsgemeinschaft (KFO 136). Professor Helmut Drexler died during the writing of this article. His premature death is a tragic loss to all those who knew him and to the field of Cardiology.

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  1. Department of Cardiology and Angiology, Hans-Borst Center for Heart and Stem Cell Research, Hannover Medical School, Carl-Neuberg-Straβe 1, Hannover, 30625, Germany

    Kai C. Wollert & Helmut Drexler

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  1. Kai C. Wollert
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Correspondence to Kai C. Wollert.

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Wollert, K., Drexler, H. Cell therapy for the treatment of coronary heart disease: a critical appraisal. Nat Rev Cardiol 7, 204–215 (2010). https://doi.org/10.1038/nrcardio.2010.1

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