Abstract
Β-blockers (BB) are a primary treatment for chronic heart disease (CHD), resulting in prognostic and symptomatic benefits. Cardiac cell therapy represents a promising regenerative treatment and, for autologous cell therapy, the patients clinical history may correlate with the biology of resident progenitors and the quality of the final cell product. This study aimed at uncovering correlations between clinical records of biopsy-donor CHD patients undergoing cardiac surgery and the corresponding yield and phenotype of cardiospheres (CSs) and CS-derived cells (CDCs), which are a clinically relevant population for cell therapy, containing progenitors. We describe a statistically significant association between BB therapy and improved CSs yield and CDCs phenotype. We show that BB-CDCs have a reduced fibrotic-like CD90 + subpopulation, with reduced expression of collagen-I and increased expression of cardiac genes, compared to CDCs from non-BB donors. Moreover BB-CDCs had a distinctive microRNA expression profile, consistent with reduced fibrotic features (miR-21, miR-29a/b/c downregulation), and enhanced regenerative potential (miR-1, miR-133, miR-101 upregulation) compared to non-BB. In vitro adrenergic pharmacological treatments confirmed cytoprotective and anti-fibrotic effects of β1-blocker on CDCs. This study shows anti-fibrotic and pro-commitment effects of BB treatment on endogenous cardiac reparative cells, and suggests adjuvant roles of β-blockers in cell therapy applications.
Highlights
Cardiovascular diseases (CVDs), encompassing myocardial infarction (MI), heart failure, and stroke, are a leading cause of mortality and morbidity worldwide, accounting for 17 million deaths per year
We considered the cumulative yield of CS-forming explant-derived cells (EDCs) per milligram of plated tissue for each biopsy as a continuous parameter
In the scenario of autologous cardiac cell therapy clinical application, it is of great translational interest to assess how the medical background and pharmacological history of potentially eligible patients might influence the biology and the successful isolation of cardiosphere-derived cells (CDCs), currently among the most promising therapeutic cell products under clinical investigation[9,20]
Summary
Cardiovascular diseases (CVDs), encompassing myocardial infarction (MI), heart failure, and stroke, are a leading cause of mortality and morbidity worldwide, accounting for 17 million deaths per year. Among the most innovative therapeutic strategies for CVDs proposed in recent years, cardiac progenitor cell (CPC) therapy has received extensive attention as a promising treatment from pre-clinical and early clinical evidence suggesting the potential to directly regenerate cardiac tissue and to activate endogenous repair, for resident CPCs9–12. Resident progenitors of most cardiovascular disease patients are naturally exposed in situ to multiple risk factors and elective drugs which are likely to modulate their biological features. This appears to represent a key issue to be considered in autologous strategies for the quality of the final cell product because cell number and regenerative potency are among the relevant factors affecting the success of cell therapy protocols[27,28,29]. The impact of drug prescriptions and potential risk factors on resident cardiac progenitors requires careful investigation for developments and improvements of cardiac cell therapy protocols
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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.
