Cardiac fibroblasts, embryonic

Serotonin 5-HT 2B receptor HTR2B Agonism Cardiac valvulopathy, fibroblast mitogenesis, hypertension. Antagonism No side effects clearly defined, but cardiac effects cannot be excluded, especially at embryonic stage. 

The EST has been developed with the aim to exploit the characteristics and differentiation potential of mouse embryonic stem cells (ES cells), established from the early embryo in 1981 [4, 5], ES cells are cultured in suspension to induce the formation of embryoid bodies, and afterwards they are transferred in 24-well dishes to allow attachment and differentiation in contracting cardiomyocytes. The toxicological endpoint is the inhibition of cardiac differentiation. In parallel a cytotoxicity test is performed on undifferentiated ES cells and a control somatic (fibroblast) cell line (3T3). The concentrations of testing chemicals that induce 50 % of differentiation inhibition (ID50) and 50 % cytotoxicity (IC50) in ES cells and 3T3 cells are inserted in a validated prediction model to classify the test chemical as non-embryotoxic, moderate, or strong embryotoxic [2, 6, 7], The validation of the method has been... 

Surprisingly, the use of cocultures with degradable PUs in cardiac TE systems has been limited when vascular grafts are excluded from the research. A study by Parrag et al. used murine-derived embryonic stem cells (mESCs) and mouse embryonic fibroblasts (MEEs) to TE cardiomyocyte-derived tissues. mESCs are pluripotent cells that require proper cues to differentiate into specific cell types. In the study, Parrag et al. showed that both the coculture of mESCs with MEEs and the use of aligned microfi-brous PU scaffolds provided the cues necessary to induce mESC differentiation to a functioning cardiomyocyte phenotype [104]. 

Parrag IC, Zandstra PW, Woodhouse KA. Fiber alignment and cocnltnre with fibroblasts improves the differentiated phenotype of murine embryonic stem cell-derived cardiomyocytes for cardiac tissne engineering. Biotechnol Bioeng March 2012 109(3) 813-22. 

Mima, T., H. Ueno, D. A. Fischman et al. 1995. Fibroblast growth factor receptor is required for in vivo cardiac myocyte proliferation at early embryonic stages of heart development. Proc Natl Acad Sci USA 92(2) 467-71. 

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