title: 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.
authors.affiliation: *Department of Cardiovascular Surgery, Pompidou Hospital, Paris, France. j.chachques@brs.aphp.fr
authors.forename: Juan C
authors.initials: JC
authors.lastname: Chachques
authors.forename: Jorge C
authors.initials: JC
authors.lastname: Trainini
authors.forename: Noemi
authors.initials: N
authors.lastname: Lago
authors.forename: Osvaldo H
authors.initials: OH
authors.lastname: Masoli
authors.forename: Jose L
authors.initials: JL
authors.lastname: Barisani
authors.forename: Miguel
authors.initials: M
authors.lastname: Cortes-Morichetti
authors.forename: Olivier
authors.initials: O
authors.lastname: Schussler
authors.forename: Alain
authors.initials: A
authors.lastname: Carpentier
mesh_terms: D020341:Absorbable Implants; D016026:Bone Marrow Transplantation / Q000009:adverse effects / Q000379:methods*; D006348:Cardiac Surgical Procedures / Q000379:methods; D024042:Collagen Type I; D005109:Extracellular Matrix / Q000737:chemistry; D005240:Feasibility Studies; D005500:Follow-Up Studies; D006801:Humans; D007902:Length of Stay; D008875:Middle Aged; D008954:Models, Biological; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D013223:Statistics as Topic; D013997:Time Factors; D054457:Tissue Scaffolds; D014185:Transplantation, Isogeneic; D016896:Treatment Outcome
chemical_list: D024042:Collagen Type I