Myocardial regeneration and asistance combined cardiac tissue engineering and stem cell therapy Outcome of trial MAGNUM

Objectives. Stem cell therapy for myocardial regeneration is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is pathologically modified, therefore it could be important to associate a procedure aiming at regenerating both, myocardial cells and the extracellular matrix. We evaluated intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted hearts. Methods. In 15 patients (aged 54.2 +/- 3.8 years) presenting LV postischemic myocardial scars and with indication for a single off-pump-CABG, autologous mononuclear bone marrow cells (BMC) were implanted during surgery in the scar. A 3D collagen type I matrix seeded with the same number of BMC was grafted onto the infarction zone. Results. There was no mortality and any related adverse events (follow-up 15 +/- 4.2 months). NYHA FC improved from 2.3 +/- 0.5 to 1.4 +/- 0.3 (p=0.005). LV end-diastolic volume evolved from 142 +/- 24 to 117 +/- 21 mL (p=0.03), LV filling deceleration time improved from 162 +/- 7 ms to 196 +/- 8 ms (p=0.01). Scar area thickness progress from 6 +/- 1.4 to 9 +/- 1.5mm (p=0.005). EF improved from 25 +/- 7 to 33 +/- 5% (p=0.04). Conclusions. Simultaneous intramyocardial injection of mononuclear bone marrow cells and fixation of a BMC-seeded matrix onto the epicardium is feasible and safe. The cell seeded collagen matrix seems to increase the thickness of the infarct scar with viable tissues and help to normalize cardiac wall stress in injured regions, thus limiting ventricular remodelling and improving diastolic function. Patients' improvements can not be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering should extend the indications and benefits of stem cell therapy in cardiology, becoming a promising way for the creation of a "bioartificial myocardium".