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Cardiac Stem Cell Therapy Revisited

Commented by Wolfgang A. Linke

Basic Science - Cardiac Diseases - Ischemia, Infarction, Cardioprotection
Gene Therapy, Cell Therapy
Treatment

Clinical trials using adult stem cells to regenerate damaged heart tissue continue to this day1,2 despite ongoing questions of efficacy and a lack of mechanistic understanding of the underlying biologic effect3. The rationale for these cell therapy trials is derived from animal studies that show a modest but reproducible improvement in cardiac function in models of cardiac ischemic injury4,5. In this new study, scientists examine the mechanistic basis for cell therapy in mice after ischemia/reperfusion (I/R) injury. They find that, while heart function was enhanced, it was not associated with new cardiomyocyte production. Cell therapy improved heart function through an acute sterile immune response characterized by the temporal and regional induction of CCR2+ and CX3CR1+ macrophages. Intra-cardiac injection of 2 distinct types of adult stem cells, freeze/thaw-killed cells or a chemical inducer of the innate immune response similarly induced regional CCR2+ and CX3CR1+ macrophage accumulation and provided functional rejuvenation to the I/R-injured heart. This selective macrophage response altered cardiac fibroblast activity, reduced border zone extracellular matrix (ECM) content, and enhanced the mechanical properties of the injured area. The authors conclude that the functional benefit of cardiac cell therapy is thus due to an acute inflammatory-based wound healing response that rejuvenates the mechanical properties of the infarcted area of the heart.

References


  1. 1. Nguyen, P. K., Rhee, J. W. & Wu, J. C. Adult Stem Cell Therapy and Heart Failure, 2000 to 2016: A Systematic Review. JAMA Cardiol 1, 831-841 (2016).
  2. 2. Fernandez-Aviles, F. et al. Global position paper on cardiovascular regenerative medicine. Eur Heart J 38, 2532-2546 (2017).
  3. 3. Epstein, J. A. A Time to Press Reset and Regenerate Cardiac Stem Cell Biology. JAMA Cardiol 4, 95-96 (2019).
  4. 4. Zwetsloot, P. P. et al. Cardiac Stem Cell Treatment in Myocardial Infarction: A Systematic Review and Meta-Analysis of Preclinical Studies. Circ Res 118, 1223-1232 (2016).
  5. 5. Tompkins, B. A. et al. Preclinical Studies of Stem Cell Therapy for Heart Disease. Circ Res 122, 1006-1020 (2018).

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.