Composite scaffold provides a cell delivery platform for cardiovascular repair

• Published in: Proceedings of the National Academy of Sciences - PNAS 2011-05, Vol.108 (19), p.7974-7979
• Main Authors: Godier-Furnémont, Amandine F.G, Martens, Timothy P, Koeckert, Michael S, Wan, Leo, Parks, Jonathan, Arai, Kotaro, Zhang, Geping, Hudson, Barry, Homma, Shunichi, Vunjak-Novakovic, Gordana
• Format: Article
• Language: English
• Subjects: Angiogenesis; animal models; Animals; Biological Sciences; Bone marrow; Cells; Disease Models, Animal; echocardiography; extracellular matrix; Extracellular Matrix - chemistry; Fibrin; Gene expression; Heart; Heart attacks; Humans; hydrocolloids; Hydrogels; infarction; Matrix; Mechanical properties; Mesenchymal Stem Cell Transplantation; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - physiology; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Infarction - therapy; Myocardium; Myocardium - chemistry; Neovascularization, Physiologic; Rats; Rats, Nude; Receptors; Rodents; Scaffolds; secretion; Stem cells; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds; transforming growth factor beta; Transforming Growth Factor beta - pharmacology; Transplantation, Heterologous; Ultrasonic imaging; Ventricular Function, Left
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1104619108

Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell-matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.