Asistencia y regeneración del miocardio combinando terapia celular e ingeniería de tejidos. Resultados del estudio clínico MAGNUM / Myocardial regeneration and asistance combined cardiac tissue engineering and stem cell therapy. Outcome of trial MAGNUM

RESUMEN

Objetivos. El trasplante celular para la regeneración del miocardio está limitado por la escasa viabilidad del injerto y la baja retención celular. En la miocardiopatía isquémica la matriz extracelular está profundamente alterada, por consiguiente, sería importante asociar un procedimiento para regenerar las células miocárdicas y restaurar la función de la matriz extracelular. En este estudio clínico, fue evaluada la terapia celular intrainfarto asociada a una matriz de colágeno sembrada con células e implantada sobre ventrículos infartados.Métodos. En 15 pacientes (54,2±3,8 años de edad) que presentaban cicatrices miocárdicas postisquémicas en el ventrículo izquierdo (VI) y con indicación de cirugía de revascularización miocárdica, se implantaron, durante la operación, células de la médula ósea mononucleares autólogas (CMO) en la cicatriz. Se agregó sobre esa zona infartada una matriz de colágeno tipo I con el mismo número de CMO

ABSTRACT

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”