Development of cardiac support bioprostheses for ventricular restoration and myocardial regeneration

• Published in: European journal of cardio-thoracic surgery 2013-06, Vol.43 (6), p.1211-1219
• Main Authors: Shafy, Abdel, Fink, Trine, Zachar, Vladimir, Lila, Nermine, Carpentier, Alain, Chachques, Juan C.
• Format: Article
• Language: English
• Subjects: Adipose Tissue - cytology; Animals; Bioprosthesis; Cardiac Surgical Procedures - methods; Collagen; Echocardiography, Doppler; Female; Heart Ventricles - surgery; Immunohistochemistry; Myocardial Infarction - surgery; Myocardium; Random Allocation; Sheep; Statistics, Nonparametric; Stem Cell Transplantation - methods; Stroke Volume - physiology; Tissue Engineering - methods; Tissue Scaffolds; Ventricular Function - physiology
• ISSN: 1010-7940; 1873-734X
• DOI: 10.1093/ejcts/ezs480

OBJECTIVES Ventricular constraint devices made of polyester and nitinol have been used to treat heart failure patients. Long-term follow-up has not demonstrated significant benefits, probably due to the lack of effects on myocardial tissue and to the risk of diastolic dysfunction. The goal of this experimental study is to improve ventricular constraint therapy by associating stem cell intrainfarct implantation and a cell-seeded collagen scaffold as an interface between the constraint device and the epicardium. METHODS In a sheep ischaemic model, three study groups were created: Group 1: coronary occlusion without treatment (control group). Group 2: postinfarct ventricular constraint using a polyester device (Acorn CorCap). Group 3: postinfarct treatment with stem cells associated with collagen matrix and the polyester device. Autologous adipose mesenchymal stem cells cultured in hypoxic conditions were injected into the infarct and seeded into the collagen matrix. RESULTS At 3 months, echocardiography showed the limitation of left ventricular end-diastolic volume in animals both treated with constraint devices alone and associated with stem cells/collagen. In Group 3 (stem cell + collagen treatment), significant improvements were found in ejection fraction (EF) and diastolic function evaluated by Doppler-derived mitral deceleration time. In this group, histology showed a reduction of infarct size, with focuses of angiogenesis and minimal fibrosis interface between CorCap and the epicardium due to the interposition of the collagen matrix. CONCLUSIONS Myocardial infarction treated with stem cells associated with a collagen matrix and ventricular constraint device improves systolic and diastolic function, reducing adverse remodelling and fibrosis. The application of bioactive molecules and the recent development of nanobiotechnologies should open the door for the creation of a new semi-degradable ventricular support bioprosthesis, capable of controlled stability or degradation in response to physiological conditions of the left or right heart.