: The adult heart displays poor reparative capacities after injury. Cell transplantation and tissue engineering approaches have emerged as possible therapeutic options. Several stem cell populations have been largely used to treat the infarcted myocardium. Nevertheless, transplanted cells displayed limited ability to establish functional connections with the host cardiomyocytes. In this study, we provide a new experimental tool, named 3D eX vivo muscle engineered tissue (X-MET), to define the contribution of mechanical stimuli in triggering functional remodeling and to rescue cardiac ischemia. We revealed that mechanical stimuli trigger a functional remodeling of the 3D skeletal muscle system toward a cardiac muscle-like structure. This was supported by molecular and functional analyses, demonstrating that remodeled X-MET expresses relevant markers of functional cardiomyocytes, compared to unstimulated and to 2D- skeletal muscle culture system. Interestingly, transplanted remodeled X-MET preserved heart function in a murine model of chronic myocardial ischemia and increased survival of transplanted injured mice. X-MET implantation resulted in repression of pro-inflammatory cytokines, induction of anti-inflammatory cytokines, and reduction in collagen deposition. Altogether, our findings indicate that biomechanical stimulation induced a cardiac functional remodeling of X-MET, which showed promising seminal results as a therapeutic product for the development of novel strategies for regenerative medicine.

Remodeled eX vivo muscle engineered tissue improves heart function after chronic myocardial ischemia / Cosentino, Marianna; Nicoletti, Carmine; Valenti, Valentina; Schirone, Leonardo; Di Nonno, Flavio; Apa, Ludovica; Zouhair, Mariam; Genovese, Desiree; Madaro, Luca; Dinarelli, Simone; Rossi, Marco; Del Prete, Zaccaria; Sciarretta, Sebastiano; Frati, Giacomo; Rizzuto, Emanuele; Musarò, Antonio. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 13:1(2023), pp. 1-15. [10.1038/s41598-023-37553-8]

Remodeled eX vivo muscle engineered tissue improves heart function after chronic myocardial ischemia

Cosentino, Marianna
Primo
;
Nicoletti, Carmine;Valenti, Valentina;Schirone, Leonardo;Di Nonno, Flavio;Apa, Ludovica;Zouhair, Mariam;Genovese, Desiree;Madaro, Luca;Dinarelli, Simone;Rossi, Marco;Del Prete, Zaccaria;Sciarretta, Sebastiano;Frati, Giacomo;Rizzuto, Emanuele;Musarò, Antonio
Ultimo
Conceptualization
2023

Abstract

: The adult heart displays poor reparative capacities after injury. Cell transplantation and tissue engineering approaches have emerged as possible therapeutic options. Several stem cell populations have been largely used to treat the infarcted myocardium. Nevertheless, transplanted cells displayed limited ability to establish functional connections with the host cardiomyocytes. In this study, we provide a new experimental tool, named 3D eX vivo muscle engineered tissue (X-MET), to define the contribution of mechanical stimuli in triggering functional remodeling and to rescue cardiac ischemia. We revealed that mechanical stimuli trigger a functional remodeling of the 3D skeletal muscle system toward a cardiac muscle-like structure. This was supported by molecular and functional analyses, demonstrating that remodeled X-MET expresses relevant markers of functional cardiomyocytes, compared to unstimulated and to 2D- skeletal muscle culture system. Interestingly, transplanted remodeled X-MET preserved heart function in a murine model of chronic myocardial ischemia and increased survival of transplanted injured mice. X-MET implantation resulted in repression of pro-inflammatory cytokines, induction of anti-inflammatory cytokines, and reduction in collagen deposition. Altogether, our findings indicate that biomechanical stimulation induced a cardiac functional remodeling of X-MET, which showed promising seminal results as a therapeutic product for the development of novel strategies for regenerative medicine.
2023
tissue engineering; cardiac regeneration; muscle remodeling; Myocardial infarction
01 Pubblicazione su rivista::01a Articolo in rivista
Remodeled eX vivo muscle engineered tissue improves heart function after chronic myocardial ischemia / Cosentino, Marianna; Nicoletti, Carmine; Valenti, Valentina; Schirone, Leonardo; Di Nonno, Flavio; Apa, Ludovica; Zouhair, Mariam; Genovese, Desiree; Madaro, Luca; Dinarelli, Simone; Rossi, Marco; Del Prete, Zaccaria; Sciarretta, Sebastiano; Frati, Giacomo; Rizzuto, Emanuele; Musarò, Antonio. - In: SCIENTIFIC REPORTS. - ISSN 2045-2322. - 13:1(2023), pp. 1-15. [10.1038/s41598-023-37553-8]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1685226
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