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VIEWPOINT

The Dying Stem Cell Hypothesis

Immune Modulation as a Novel Mechanism for Progenitor Cell Therapy in Cardiac Muscle

Thomas Thum, MD^_*,,_*, Johann Bauersachs, MD, Philip A. Poole-Wilson, MD, FRCP^_*, Hans-Dieter Volk, MD, PhD and Stefan D. Anker, MD, PhD^_*,,_*

^_* Department of Clinical Cardiology, National Heart and Lung Institute, Imperial College of Medicine, London, United Kingdom
Medizinische Klinik I, Universitätsklinikum, Bayerische Julius-Maximilians-Universität, Würzburg, Germany
Institute of Medical Immunology, Charité Campus Mitte, Berlin, Germany
Applied Cachexia Research, Department of Cardiology, Charité Campus Virchow-Klinikum, Berlin, Germany

Manuscript received June 3, 2005; revised manuscript received July 1, 2005, accepted July 12, 2005.

^_* Reprint requests and correspondence: Dr. Thomas Thum, Julius-Maximilians University, Cardiology, Josef-Schneider Str. 2, Würzburg, Bavaria 97080, Germany. (Email: thum_t{at}klinik.uni-wuerzburg.de).

^_* Prof. Stefan Anker, National Heart and Lung Institute, Department of Clinical Cardiology, Dovehouse Street, London SW3 6LY, United Kingdom. (Email: s.anker{at}imperial.ac.uk).

Stem cell transplantation after myocardial infarction has been claimed to restore cardiac function, but the underlying mechanism remains unclear. A minority of transplanted cells become adherent in heart tissue and contribute to neovascularization, whereas many donor cells die from apoptosis. We propose that apoptosis of transplanted cells modulates local tissue reactions. Apoptotic cells impact on immune reactivity by down-regulating innate and adaptive immunity, deactivating macrophages and dendritic cells, and stimulating regulatory T cells. This leads to reduced scar formation, repressed myocardial apoptosis, and improved cardiac outcome.

Abbreviations and Acronyms   AMI = acute myocardial infarction   IL = interleukin   PS = phosphatidylserine   TGF = transforming growth factor   TLR = Toll-like receptor

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