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Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

by Carolina Balbi 1,†, Ambra Costa 2,†, Lucio Barile 3,4,*,‡ and Sveva Bollini 2,*,‡
Laboratory of Cellular and Molecular Cardiology, Cardiocentro Ticino Foundation, 6900 Lugano, Switzerland
Regenerative Medicine Laboratory, Dept. of Experimental Medicine (DIMES), University of Genova, 16132 Genova, Italy
Laboratory for Cardiovascular Theranostics, Cardiocentro Ticino Foundation, 6900 Lugano, Switzerland
Faculty of Biomedical Sciences, Università della Svizzera Italiana, 6900 Lugano, Switzerland
Authors to whom correspondence should be addressed.
Joint contribution.
Joint contribution.
Cells 2020, 9(3), 724;
Received: 8 January 2020 / Revised: 5 March 2020 / Accepted: 12 March 2020 / Published: 15 March 2020
(This article belongs to the Special Issue Therapeutic Applications of Extracellular Vesicles)
Ischaemic cardiac disease is associated with a loss of cardiomyocytes and an intrinsic lack of myocardial renewal. Recent work has shown that the heart retains limited cardiomyocyte proliferation, which remains inefficient when facing pathological conditions. While broadly active in the neonatal mammalian heart, this mechanism becomes quiescent soon after birth, suggesting loss of regenerative potential with maturation into adulthood. A key question is whether this temporary regenerative window can be enhanced via appropriate stimulation and further extended. Recently the search for novel therapeutic approaches for heart disease has centred on stem cell biology. The “paracrine effect” has been proposed as a promising strategy to boost endogenous reparative and regenerative mechanisms from within the cardiac tissue by exploiting the modulatory potential of soluble stem cell-secreted factors. As such, growing interest has been specifically addressed towards stem/progenitor cell-secreted extracellular vesicles (EVs), which can be easily isolated in vitro from cell-conditioned medium. This review will provide a comprehensive overview of the current paradigm on cardiac repair and regeneration, with a specific focus on the role and mechanism(s) of paracrine action of EVs from cardiac stromal progenitors as compared to exogenous stem cells in order to discuss the optimal choice for future therapy. In addition, the challenges to overcoming translational EV biology from bench to bedside for future cardiac regenerative medicine will be discussed. View Full-Text
Keywords: paracrine effect; extracellular vesicles; exosomes; cardiac repair; angiogenesis; myocardial renewal; regeneration paracrine effect; extracellular vesicles; exosomes; cardiac repair; angiogenesis; myocardial renewal; regeneration
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Balbi, C.; Costa, A.; Barile, L.; Bollini, S. Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation. Cells 2020, 9, 724.

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