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

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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.

Keywords: Bioartificial myocardium; Cellular cardiomyoplasty; Heart failure; Ischemic heart disease; Myocardial regeneration; Stem cell therapy; Tissue engineering

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368907783338217

Affiliations: 1: Department of Cardiovascular Surgery, Pompidou Hospital, Paris, France 2: Avellaneda Hospital, Buenos Aires, Argentina

Publication date: September 1, 2007

More about this publication?
  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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