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

Isotta Chimenti, Francesca Pagano, Elena Cavarretta, Francesco Angelini, Mariangela Peruzzi, Antonio Barretta, Ernesto Greco, Elena De Falco, Antonino G M Marullo, Sebastiano Sciarretta, Giuseppe Biondi-Zoccai, Giacomo Frati

Research output: Contribution to journalArticle

Abstract

B-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.

Original languageEnglish
Article number36774
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Nov 14 2016

Fingerprint

Patient Isolation
Thoracic Surgery
Phenotype
Cell- and Tissue-Based Therapy
Therapeutics
Heart Diseases
Chronic Disease
Tissue Donors
MicroRNAs
Adrenergic Agents
Up-Regulation
Collagen
Down-Regulation
Pharmacology
Biopsy
Gene Expression

ASJC Scopus subject areas

  • General

Cite this

B-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 G M; Sciarretta, Sebastiano; Biondi-Zoccai, Giuseppe; Frati, Giacomo.

In: Scientific Reports, Vol. 6, 36774, 14.11.2016.

Research output: Contribution to journalArticle

Chimenti, I, Pagano, F, Cavarretta, E, Angelini, F, Peruzzi, M, Barretta, A, Greco, E, De Falco, E, Marullo, AGM, Sciarretta, S, Biondi-Zoccai, G & Frati, G 2016, 'B-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells', Scientific Reports, vol. 6, 36774. https://doi.org/10.1038/srep36774
Chimenti, Isotta ; Pagano, Francesca ; Cavarretta, Elena ; Angelini, Francesco ; Peruzzi, Mariangela ; Barretta, Antonio ; Greco, Ernesto ; De Falco, Elena ; Marullo, Antonino G M ; Sciarretta, Sebastiano ; Biondi-Zoccai, Giuseppe ; Frati, Giacomo. / B-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells. In: Scientific Reports. 2016 ; Vol. 6.
@article{45c94d57e8d5468c9e1cff084618442c,
title = "B-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells",
abstract = "B-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.",
author = "Isotta Chimenti and Francesca Pagano and Elena Cavarretta and Francesco Angelini and Mariangela Peruzzi and Antonio Barretta and Ernesto Greco and {De Falco}, Elena and Marullo, {Antonino G M} and Sebastiano Sciarretta and Giuseppe Biondi-Zoccai and Giacomo Frati",
year = "2016",
month = "11",
day = "14",
doi = "10.1038/srep36774",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - B-blockers treatment of cardiac surgery patients enhances isolation and improves phenotype of cardiosphere-derived cells

AU - Chimenti, Isotta

AU - Pagano, Francesca

AU - Cavarretta, Elena

AU - Angelini, Francesco

AU - Peruzzi, Mariangela

AU - Barretta, Antonio

AU - Greco, Ernesto

AU - De Falco, Elena

AU - Marullo, Antonino G M

AU - Sciarretta, Sebastiano

AU - Biondi-Zoccai, Giuseppe

AU - Frati, Giacomo

PY - 2016/11/14

Y1 - 2016/11/14

N2 - B-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.

AB - B-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.

UR - http://www.scopus.com/inward/record.url?scp=84995503421&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84995503421&partnerID=8YFLogxK

U2 - 10.1038/srep36774

DO - 10.1038/srep36774

M3 - Article

AN - SCOPUS:84995503421

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 36774

ER -