title: Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells.
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.
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Isotta
authors.initials: I
authors.lastname: Chimenti
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pagano
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cavarretta
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelini
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Peruzzi
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological, and Geriatric Sciences, "Umberto I" Hospital, "La Sapienza" University of Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Barretta
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological, and Geriatric Sciences, "Umberto I" Hospital, "La Sapienza" University of Rome, Italy.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Greco
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: De Falco
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.
authors.forename: Antonino G M
authors.initials: AG
authors.lastname: Marullo
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.|Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Sciarretta
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.|Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Department of Medical Surgical Sciences and Biotechnology, "La Sapienza" University of Rome, Italy.|Department of AngioCardioNeurology, IRCCS Neuromed, Pozzilli, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Frati
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D000368:Aged; D049109:Cell Proliferation; D002469:Cell Separation; D002478:Cells, Cultured; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006331:Heart Diseases / Q000188:drug therapy / Q000473:pathology / Q000601:surgery; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology; D010641:Phenotype; D018874:Spheroids, Cellular / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D035683:MicroRNAs