Functional and histopathological improvement of the post-infarcted rat heart upon myoblast cell grafting and relaxin therapy
Massimo Bonacchi
Department of Medical and Surgical Critical Area, Cardiac Surgery Unit, University of Florence, Florence, Italy
M.B and S.N. contributed equally to this article.
Search for more papers by this authorSilvia Nistri
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
M.B and S.N. contributed equally to this article.
Search for more papers by this authorCristina Nanni
Nuclear Medicine Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorSandro Gelsomino
Experimental Surgery Unit, Careggi Hospital, Florence, Italy
Search for more papers by this authorAlessandro Pini
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorLorenzo Cinci
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorMassimo Maiani
Department of Medical and Surgical Critical Area, Cardiac Surgery Unit, University of Florence, Florence, Italy
Search for more papers by this authorSandra Zecchi-Orlandini
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorRoberto Lorusso
Experimental Surgery Unit, Careggi Hospital, Florence, Italy
Search for more papers by this authorStefano Fanti
Nuclear Medicine Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorJosh Silvertown
Ontario Cancer Institute, University Health Network, Toronto, Canada
Search for more papers by this authorCorresponding Author
Daniele Bani
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Correspondence to: Prof. Daniele BANI,Department of Anatomy, Histology & Forensic Medicine,University of Florence,viale G.Pieraccini, 6I-50139, Florence, Italy.Tel.: +39-0554271390Fax: +39-0554271385E-mail: [email protected]Search for more papers by this authorMassimo Bonacchi
Department of Medical and Surgical Critical Area, Cardiac Surgery Unit, University of Florence, Florence, Italy
M.B and S.N. contributed equally to this article.
Search for more papers by this authorSilvia Nistri
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
M.B and S.N. contributed equally to this article.
Search for more papers by this authorCristina Nanni
Nuclear Medicine Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorSandro Gelsomino
Experimental Surgery Unit, Careggi Hospital, Florence, Italy
Search for more papers by this authorAlessandro Pini
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorLorenzo Cinci
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorMassimo Maiani
Department of Medical and Surgical Critical Area, Cardiac Surgery Unit, University of Florence, Florence, Italy
Search for more papers by this authorSandra Zecchi-Orlandini
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Search for more papers by this authorRoberto Lorusso
Experimental Surgery Unit, Careggi Hospital, Florence, Italy
Search for more papers by this authorStefano Fanti
Nuclear Medicine Unit, S.Orsola-Malpighi Hospital, Bologna, Italy
Search for more papers by this authorJosh Silvertown
Ontario Cancer Institute, University Health Network, Toronto, Canada
Search for more papers by this authorCorresponding Author
Daniele Bani
Department of Anatomy, Histology & Forensic Medicine, University of Florence, Florence, Italy
Correspondence to: Prof. Daniele BANI,Department of Anatomy, Histology & Forensic Medicine,University of Florence,viale G.Pieraccini, 6I-50139, Florence, Italy.Tel.: +39-0554271390Fax: +39-0554271385E-mail: [email protected]Search for more papers by this authorAbstract
Although the myocardium contains progenitor cells potentially capable of regenerating tissue upon lethal ischaemic injury, their actual role in post-infarction heart healing is negligible. Therefore, transplantation of extra-cardiac stem cells is a promising therapeutic approach for post-infarction heart dysfunction. Paracrine cardiotropic factors released by the grafted cells, such as the cardiotropic hormone relaxin (RLX), may beneficially influence remodelling of recipient hearts. The current study was designed to address whether grafting of mouse C2C12 myoblasts, genetically engineered to express green fluorescent protein (C2C12/GFP) or GFP and RLX (C2C12/RLX), are capable of improving long-term heart remodelling in a rat model of surgically induced chronic myocardial infarction. One month after myocardial infarction, rats were treated with either culture medium (controls), or C2C12/GFP cells, or C2C12/RLX cells plus exogenous RLX, or exogenous RLX alone. The therapeutic effects were monitored for 2 further months. Cell transplantation and exogenous RLX improved the main echocardiographic parameters of cardiac function, increased myocardial viability (assessed by positron emission tomography), decreased cardiac sclerosis and myocardial cell apoptosis and increased microvascular density in the post-infarction scar tissue. These effects were maximal upon treatment with C2C12/RLX plus exogenous RLX. These functional and histopathological findings provide further experimental evidence that myoblast cell grafting can improve myocardial performance and survival during post-infarction heart remodelling and dysfunction. Further, this study provides a proof-of-principle to the novel concept that genetically engineered grafted cells can be effectively employed as cell-based vehicles for the local delivery of therapeutic cardiotropic substances, such as RLX, capable of improving adverse heart remodelling.
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