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Cell-enhancement strategies for the treatment of ischemic heart disease

Nature Clinical Practice Cardiovascular Medicine volume 4, pages S110–S113 (2007)Cite this article

Abstract

Cell therapy is a promising option for the treatment of ischemic diseases. Infusion or injection of stem or progenitor cells has improved neovascularization and heart function after ischemia in various experimental studies and clinical phase II and III trials. One potential limitation for cell therapy is a low rate of engraftment and persistence of cells in the ischemic tissue. Moreover, impairment of the number and function of patient-derived progenitor cells might limit the efficiency of autologous stem cell therapy. Therefore, strategies to augment cell function, survival, and homing could be crucial to improve success rates for cell therapy. Experimental studies have provided novel options for improving survival and function by transduction of stem or progenitor cells with prosurvival genes (e.g. Akt or telomerase). Pretreatment of cells with small molecules, such as statins, p38 inhibitors, or endothelial nitric oxide synthase enhancers, has been used to augment cell homing, integration, and functional recovery after induction of ischemia. Priming of the tissue by mechanical activation or application of growth factors might further improve recruitment and incorporation of cells. In this article we summarize the experimental studies providing novel concepts for cell-enhancement strategies to aid the treatment of peripheral artery occlusive and ischemic heart disease.

Key Points

  • Cell therapy is a promising option in the treatment of ischemic diseases

  • Circulating and bone marrow-derived progenitor cells from patients with coronary artery disease are impaired in function

  • Augmentation of the functional activity of patient-derived cells may improve the efficiency of autologous cell therapy

  • Strategies to augment homing, survival, and incorporation of infused or injected progenitor cells may increase the functional benefit of cell therapy

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Figure 1: Stem cell enhancement strategies to treat ischemic heart disease

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Authors and Affiliations

  1. FH Seeger is a physician scientist, AM Zeiher is Director of Medicine, Clinic III, and S Dimmeler is Head of Molecular Cardiology, University of Frankfurt, Germany.,

    Florian H Seeger, Andreas M Zeiher & Stefanie Dimmeler

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  1. Florian H Seeger
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  2. Andreas M Zeiher
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  3. Stefanie Dimmeler
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Correspondence to Stefanie Dimmeler.

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Competing interests

S Dimmeler and AM Zeiher are named as co-inventors on a patent application (“Use of eNOS transcription enhancers in the cell therapy of ischemic heart diseases”) filed by Aventis Pharmaceuticals Inc. (US application #20050101599) and on a patent application (“Shock wave pretreatment as a therapeutic tool for targeted recruitment of stem/progenitor cells”) filed by Dornier MedTech Systems GmbH.

F H Seeger declared no competing interests.

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Seeger, F., Zeiher, A. & Dimmeler, S. Cell-enhancement strategies for the treatment of ischemic heart disease. Nat Rev Cardiol 4 (Suppl 1), S110–S113 (2007). https://doi.org/10.1038/ncpcardio0734

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