Myocardial Assistance by Grafting a New Bioartificial Upgraded Myocardium (MAGNUM Clinical Trial): One Year Follow-Up

Abstract

Cell transplantation for the regeneration of ischemic myocardium is limited by poor graft viability and low cell retention. In ischemic cardiomyopathy the extracellular matrix is deeply altered; therefore, it could be important to associate a procedure aiming at regenerating myocardial cells and restoring the extracellular matrix function. We evaluated intrainfarct cell therapy associated with a cell-seeded collagen scaffold grafted onto infarcted ventricles. In 15 patients (aged 54.2 +/- 3.8 years) presenting LV postischemic myocardial scars and with indication for a single OP-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 added on top of the scarred area. There was no mortality and no 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), and LV filling deceleration time improved from 162 +/- 7 to 196 +/- 8 ms (p = 0.01). Scar area thickness progressed from 6 +/- 1.4 to 9 +/- 1.5 mm (p = 0.005). EF improved from 25 +/- 7% to 33 +/- 5% (p = 0.04). 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 helps to normalize cardiac wall stress in injured regions, thus limiting ventricular remodeling and improving diastolic function. Patients' improvements cannot be conclusively related to the cells and matrix due to the association of CABG. Cardiac tissue engineering seems to extend the indications and benefits of stem cell therapy in cardiology, becoming a promising way for the creation of a "bioartificial myocardium." Efficacy and safety of this approach should be evaluated in a large randomized controlled trial.

The use of human mesenchymal stem cells encapsulated in RGD modified alginate microspheres in the repair of myocardial infarction in the rat

“…Direct injection of cells into the infracted myocardium has resulted in limited survival and retention of the transplanted cells [5,6]. Transplant survival has been increased with the induction of angiogenesis [7,8].…”

Cardiac Tissue Engineering

“…Presently one cardiac tissue engineering clinical trial has been completed using autologous bone marrow derived cells incorporated into a collagen sponge scaffold (Chachques et al, 2008). The clinical study recipients showed improvements at the one-year follow-up; however further studies are necessary to rule out confounding factors such as concomitant coronary artery bypass graft surgery (Chachques et al, 2007).…”

Predifferentiated Adult Stem Cells and Matrices for Cardiac Cell Therapy

“…33 Recently, a similar approach was used successfully in a clinical trial (MAGNUM trial) with a bone marrow mesenchymal stem cell-seeded collagen sponge applied on top of the scarred area, with the aim of regenerating myocardial cells and restoring extracellular matrix function which is deeply altered following myocardial infarction. 54,55 The MAGNUM trial is an example of the possible association between stem cell therapy and tissue engineering. Polymeric biomaterials have also been engrafted with growth factors, cytokines, and drugs, thus obtaining drug-releasing systems capable of focused and localized delivery of molecules, depending on the environmental requirements and the actual milieu in which the scaffold is placed.…”