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.

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells / Chimenti, Isotta; Pagano, Francesca; Cavarretta, Elena; Angelini, Francesco; Peruzzi, Mariangela; Barretta, Antonio; Greco, Ernesto; DE FALCO, Elena; Marullo, Antonino; Sciarretta, Sebastiano; BIONDI ZOCCAI, Giuseppe; Frati, Giacomo. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 6:(2016). [10.1038/srep36774]

Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

CHIMENTI, ISOTTA
;
PAGANO, FRANCESCA
Co-primo
;
CAVARRETTA, Elena;ANGELINI, FRANCESCO;PERUZZI, MARIANGELA;BARRETTA, ANTONIO;GRECO, Ernesto;DE FALCO, ELENA;MARULLO, Antonino;SCIARRETTA, SEBASTIANO;BIONDI ZOCCAI, GIUSEPPE;FRATI, GIACOMO
Ultimo
2016

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.
2016
to-mesenchymal transition; stem-cells; myocardial-infarction; progenitor cells; heart-failure; down-regulation; expression; regeneration; cardiomyocytes; proliferation
01 Pubblicazione su rivista::01a Articolo in rivista
Β-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells / Chimenti, Isotta; Pagano, Francesca; Cavarretta, Elena; Angelini, Francesco; Peruzzi, Mariangela; Barretta, Antonio; Greco, Ernesto; DE FALCO, Elena; Marullo, Antonino; Sciarretta, Sebastiano; BIONDI ZOCCAI, Giuseppe; Frati, Giacomo. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - ELETTRONICO. - 6:(2016). [10.1038/srep36774]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/912687
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