Cardiac disease modeling using induced pluripotent stem cell-derived human cardiomyocytes.

Causative mutations and variants associated with cardiac diseases have been found in genes encoding cardiac ion channels, accessory proteins, cytoskeletal components, junctional proteins, and signaling molecules. In most cases the functional evaluation of the genetic alteration has been carried out by expressing the mutated proteins in in-vitro heterologous systems. While these studies have provided a wealth of functional details that have greatly enhanced the understanding of the pathological mechanisms, it has always been clear that heterologous expression of the mutant protein bears the intrinsic limitation of the lack of a proper intracellular environment and the lack of pathological remodeling.

Ascorbic acid rescues cardiomyocyte development in Fgfr1(-/-) murine embryonic stem cells.

Fibroblast growth factor receptor 1 (Fgfr1) gene knockout impairs cardiomyocyte differentiation in murine embryonic stem cells (mESC). Here, various chemical compounds able to enhance cardiomyocyte differentiation in mESC [including dimethylsulfoxide, ascorbic acid (vitC), free radicals and reactive oxygen species] were tested for their ability to rescue the cardiomyogenic potential of Fgfr1(-/-) mESC. Among them, only the reduced form of vitC, l-ascorbic acid, was able to recover beating cell differentiation in Fgfr1(-/-) mESC.

Phage displayed peptides/antibodies recognizing growth factors and their tyrosine kinase receptors as tools for anti-cancer therapeutics.

The basic idea of displaying peptides on a phage, introduced by George P. Smith in 1985, was greatly developed and improved by McCafferty and colleagues at the MRC Laboratory of Molecular Biology and, later, by Barbas and colleagues at the Scripps Research Institute. Their approach was dedicated to building a system for the production of antibodies, similar to a naïve B cell repertoire, in order to by-pass the standard hybridoma technology that requires animal immunization.

Fibroblast growth factor receptor-1 phosphorylation requirement for cardiomyocyte differentiation in murine embryonic stem cells.

Fibroblast growth factor receptor-1 (Fgfr1) gene knockout impairs cardiac and haematopoietic development in murine embryonic stem cells (mESC). In FGFR1, tyrosine residues Y653 and Y654 are responsible for its tyrosine kinase (TK) activity whereas phosphorylated Y463 and Y766 represent docking sites for intracellular substrates. Aim of this study was the characterization of FGFR1 signalling requirements necessary for cardiomyocyte differentiation in mESC.