title: Distinct cell-to-fiber junctions are critical for the establishment of cardiotypical phenotype in a 3D bioartificial environment.
abstract: The first step toward improving the cell-matrix interactions that occur in bioartificial myocardial tissue is an understanding of the ultrastructural links between cells and host fibers. Here, we identify a distinct type of junction that helps the cells to find anchorage in the three-dimensional environment, and we evaluate the phenotype of the resulting tissue. Neonatal rat cardiomyocytes were seeded in two different collagen scaffolds after pre-hydration of the scaffold. Conventional and electron microscopy were used to analyze the tissue microstructure. Viability was assessed by life/dead assay and physical properties of the resulting tissue were evaluated. The resulting tissue displayed high cellular viability, spontaneous contractions over 12 weeks, and responded to passive stretch similar to native rat myocardium. Contractile force responded physiologically to calcium (Ca), adrenaline, and stretch administration. Ultrastructural studies revealed a cell-to-fiber junction, as well as a background matrix configuration, which has not been described before in this context. The cells aligned along collagen fibers and engaged in complex intercalations. The cell-to-fiber affinity is essential for the phenotypical performance of bioartificial myocardial tissue equivalents. Moreover, given the appropriate porosity of the scaffold, pre-hydration promotes migration and affinity of cells to host structures.
authors.affiliation: Department of Cardiothoracic Surgery, Falk Research Center, 2fl, Stanford University Medical School, 300 Pasteur Dr., Stanford, CA94305, USA. tkofidis@stanford.edu
authors.forename: Theo
authors.initials: T
authors.lastname: Kofidis
authors.forename: Leora
authors.initials: L
authors.lastname: Balsam
authors.forename: Jorg
authors.initials: J
authors.lastname: de Bruin
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D021522:Bioartificial Organs; D002118:Calcium / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D018929:Cell Culture Techniques / Q000379:methods; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen; D004837:Epinephrine / Q000494:pharmacology; D007365:Intercellular Junctions / Q000187:drug effects / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D013499:Surface Properties; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D003094:Collagen; D002118:Calcium; D004837:Epinephrine