Abstract
Cardiac remuscularization has been the stated goal of the field of regenerative cardiology since its inception. Along with the refreshment of lost and dysfunctional cardiac muscle cells, the field of cell therapy has expanded in scope encompassing also the potential of the injected cells as cardioprotective and cardio-reparative agents for cardiovascular diseases. The latter has been the result of the findings that cell therapies so far tested in clinical trials exert their beneficial effects through paracrine mechanisms acting on the endogenous myocardial reparative/regenerative potential. The endogenous regenerative potential of the adult heart is still highly debated. While it has been widely accepted that adult cardiomyocytes (CMs) are renewed throughout life either in response to wear and tear and after injury, the rate and origin of this phenomenon are yet to be clarified. The adult heart harbors resident cardiac/stem progenitor cells (CSCs/CPCs), whose discovery and characterization were initially sufficient to explain CM renewal in response to physiological and pathological stresses, when also considering that adult CMs are terminally differentiated cells. The role of CSCs in CM formation in the adult heart has been however questioned by some recent genetic fate map studies, which have been proved to have serious limitations. Nevertheless, uncontested evidence shows that clonal CSCs are effective transplantable regenerative agents either for their direct myogenic differentiation and for their paracrine effects in the allogeneic setting. In particular, the paracrine potential of CSCs has been the focus of the recent investigation, whereby CSC-derived exosomes appear to harbor relevant regenerative and reparative signals underlying the beneficial effects of CSC transplantation. This review focuses on recent advances in our knowledge about the biological role of exosomes in heart tissue homeostasis and repair with the idea to use them as tools for new therapeutic biotechnologies for “cell-less” effective cardiac regeneration approaches.
Highlights
Among cardiovascular disease (CVD), myocardial infarction (MI) and heart failure (HF) represent the most important heart conditions in terms of mortality, morbidity and average life expectancy [1,2,3]
The prevention and the treatment of chronic heart failure (CHF) are based on pharmacotherapy and implantation of medical devices and/or surgical interventions, to maintain or improve the performance of the pre-existing cardiomyocytes (CMs), but not to replace the injured heart with a new and functional cardiac muscle cell population, CHF is always due to a deficit of cardiomyocytes mass and function
The goal of regenerative cardiology has always been the search of a population of cells that could be safely transplanted to the patients determining an effective remuscularization of the damaged organ [11,13,19,21,54,56,57,58]
Summary
Among cardiovascular disease (CVD), myocardial infarction (MI) and heart failure (HF) represent the most important heart conditions in terms of mortality, morbidity and average life expectancy [1,2,3]. The interactions with target cells are not fully elucidated, but it could occur through different mechanisms: (1) through binding to specific receptors expressed on the surface of target cells, which can trigger a signaling mechanism and the consequent formation of a multimolecular extracellular complex; (2) by direct fusion of its membrane with that of the target cell, immediately releasing its contents inside the cell; (3) through endocytosis In the latter case, the endocytic exosome can remain segregated within endosomes and merge with lysosomes to be degraded or can melt its membrane with the endosomal one to release its contents inside the cytoplasm of the target cell or by transcytosis can reach the extracellular space following the fusion of the endosome with the plasma membrane [103]. Once released into the heart by different cell types, including exogenous transplanted stem and progenitor cells, exosomes exert cardiac protection For this reason, they have been proposed as elements that improve tissue environment after damage, a significant phenomenon to optimize survival and engraftment of cells after their transplantation [50]. It is envisioned that exosomes can be used as nanoparticles for targeted delivery of several miRNAs that can target different cellular processes, from inflammation to immune responses and from cardio-protection to cardiac regeneration, representing a novel form of gene therapy [56,111]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
