Biochim Biophys Acta Mol Cell Res
March 2020
The development of functional and reliable in vitro cardiac models composed of fully mature cardiomyocytes is essential for improving drug screening test quality, therefore, the success of clinical trial outcomes. In their lifespan, cardiomyocytes undergo a dynamic maturation process from the fetal to adult stage, radically changing their metabolism, morphology, contractility and electrical properties. Before employing cells of human origin, in vitro models often use neonatal rat cardiomyocytes (NRCM) to obtain key proof-of-principles.
View Article and Find Full Text PDFIn vitro recapitulation of an organotypic stromal environment, enabling efficient angiogenesis, is crucial to investigate and possibly improve vascularization in regenerative medicine. Our study aims at engineering the complexity of a vascular milieu including multiple cell-types, a stromal extracellular matrix (ECM), and molecular signals. For this purpose, the human adipose stromal vascular fraction (SVF), composed of a heterogeneous mix of pericytes, endothelial/stromal progenitor cells, was cultured under direct perfusion flow on three-dimensional (3D) collagen scaffolds.
View Article and Find Full Text PDFBackground: Recent studies suggest that adult cardiac progenitor cells (CPCs) can produce new cardiac cells. Such cell formation requires an intricate coordination of progenitor cell proliferation and commitment, but the molecular cues responsible for this regulation in CPCs are ill defined.
Methods And Results: Extracellular matrix components are important instructors of cell fate.
Delivery of genetically modified cells overexpressing Vascular Endothelial Growth Factor (VEGF) is a promising approach to induce therapeutic angiogenesis in ischemic tissues. The effect of the protein is strictly modulated by its interaction with the components of the extracellular matrix. Its therapeutic potential depends on a sustained but controlled release at the microenvironmental level in order to avoid the formation of abnormal blood vessels.
View Article and Find Full Text PDFUnlabelled: Therapeutic over-expression of Vascular Endothelial Growth Factor (VEGF) by transduced progenitors is a promising strategy to efficiently induce angiogenesis in ischemic tissues (e.g. limb muscle and myocardium), but tight control over the micro-environmental distribution of the dose is required to avoid induction of angioma-like tumors.
View Article and Find Full Text PDFIn the past few years, microfluidic-based technology has developed microscale models recapitulating key physical and biological cues typical of the native myocardium. However, the application of controlled physiological uniaxial cyclic strains on a defined three-dimension cellular environment is not yet possible. Two-dimension mechanical stimulation was particularly investigated, neglecting the complex three-dimensional cell-cell and cell-matrix interactions.
View Article and Find Full Text PDFThe availability of 3D sponges combining proper biochemical, biophysical, and biomechanical properties with enhanced capacity of in vivo engraftment and vascularization is crucial in regenerative medicine. A simple process is developed to generate macroporous scaffolds with a well-defined architecture of interconnected pores from chicken egg white (EW), a material with protein- and growth factor-binding features which has not yet been employed in regenerative medicine. The physicomechanical properties and degradation rates of the scaffold are finely tuned by using varying concentrations of the cross-linker, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride, without alteration of the biochemical traits.
View Article and Find Full Text PDFConventional tissue engineering strategies often rely on the use of a single progenitor cell source to engineer in vitro biological models; however, multi-cellular environments can better resemble the complexity of native tissues. Previous described co-culture models used skeletal myoblasts, as parenchymal cell source, and mesenchymal or endothelial cells, as stromal component. Here, we propose instead the use of adipose tissue-derived stromal vascular fraction cells, which include both mesenchymal and endothelial cells, to better resemble the native stroma.
View Article and Find Full Text PDF