Key result
The evolution of stem cell theory for cardiac regeneration may ultimately lead to the development of cell-free strategies targeting multiple cardiac cell types.
The review highlights the evolution of stem cell therapy for heart failure, suggesting a paradigm shift towards cell-free strategies utilizing paracrine factors like extracellular vesicles.
Cell-free strategies merit further study in heart failure; leaves open clinical translation pending prospective trials.
Various stem cell-based approaches for cardiac repair have achieved encouraging results in animal experiments, often leading to their rapid proceeding to clinical testing. However, freewheeling evolutionary developments of the stem cell theory might lead to dystopian scenarios where heterogeneous sources of therapeutic cells could promote mixed clinical outcomes in un-stratified patient populations. This review focuses on the lessons that should be learnt from the first generation of stem cell-based strategies and emphasizes the absolute requirement to better understand the basic mechanisms of stem cell biology and cardiogenesis. We will also discuss about the unexpected "big bang" in the stem cell theory, "blasting" the therapeutic cells to their unchallenged ability to release paracrine factors such as extracellular membrane vesicles. Paradoxically, the natural evolution of the stem cell theory for cardiac regeneration may end with the development of cell-free strategies with multiple cellular targets including cardiomyocytes but also other infiltrating or resident cardiac cells.
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Silvestre et al. (2015) conducted a review in Heart Failure. Stem cell-based approaches was evaluated. The evolution of stem cell theory for cardiac regeneration may ultimately lead to the development of cell-free strategies targeting multiple cardiac cell types.
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