title: Composite scaffold provides a cell delivery platform for cardiovascular repair.
abstract: 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.
authors.affiliation: Department of Biomedical Engineering, Columbia University, New York, NY 10032, USA.
authors.forename: Amandine F G
authors.initials: AF
authors.lastname: Godier-Furnémont
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Martens
authors.forename: Michael S
authors.initials: MS
authors.lastname: Koeckert
authors.forename: Leo
authors.initials: L
authors.lastname: Wan
authors.forename: Jonathan
authors.initials: J
authors.lastname: Parks
authors.forename: Kotaro
authors.initials: K
authors.lastname: Arai
authors.forename: Geping
authors.initials: G
authors.lastname: Zhang
authors.forename: Barry
authors.initials: B
authors.lastname: Hudson
authors.forename: Shunichi
authors.initials: S
authors.lastname: Homma
authors.forename: Gordana
authors.initials: G
authors.lastname: Vunjak-Novakovic
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000737:chemistry; D005337:Fibrin; D006801:Humans; D020100:Hydrogels; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000737:chemistry*; D018919:Neovascularization, Physiologic; D051381:Rats; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014183:Transplantation, Heterologous; D016277:Ventricular Function, Left
chemical_list: D020100:Hydrogels; D016212:Transforming Growth Factor beta; D005337:Fibrin