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Embryonic stem (ES) cells are revolutionizing the field of developmental biology as a potential tool to understand the molecular mechanisms occurring during the process of differentiation from the embryonic stage to the adult phenotype. ES cells harvested from the inner cell mass (ICM) of the early embryo can proliferate indefinitely in vitro while retaining the ability to differentiate into all somatic cells. Emerging results from mice models with ES cells are promising and raising tremendous hope among the scientific community for the ES-cell based cell replacement therapy (CRT) of various severe diseases. ES cells could potentially revolutionize medicine by providing an unlimited renewable source of cells capable of replacing or repairing tissues that have been damaged in almost all degenerative diseases such as diabetes, myocardial infarction and Parkinson's disease. This review updates the progress of ES cell research in CRT, discusses about the problems encountered in the practical utility of ES cells in CRT and evaluates how far this approach is successful experimentally.

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Multiple types of voltage-activated Ca(2+) channels (T, L, N, P, Q, R type) coordinate Ca(2+)-dependent processes in neurons and neuroendocrine cells. Expressional and functional data have suggested a role for Ca(v)2.3 Ca(2+) channels in endocrine processes. To verify its role in vivo, Ca(v)2.3(-/-) mutant mice were generated, thus deficient in alpha 1E/R-type Ca(2+) channel. Intraperitoneal injection of D-glucose showed that glucose tolerance was markedly reduced, and insulin release into plasma was impaired in Ca(v)2.3-deficient mice. In isolated islets of Langerhans from these animals, no glucose-induced insulin release was detected. Further, in stressed Ca(v)2.3-deficient mice, the rate of glucose release into the blood was only 29% of that observed for wild-type animals. Thus, the deletion of Ca(v)2.3 causes deficits not only in insulin release but also in stress-induced hyperglycemia. The complex phenotype of Ca(v)2.3-deficient mice has dual components related to endocrine and neurological defects. The present findings provide direct evidence of a functional role for the Ca(v)2.3 subunit in hormone secretion and glucose homeostasis.

Background/Aims: Embryonic stem (ES) cells may represent an alternative source of functionally mature cardiomyocytes for the treatment of heart diseases. ES cells spontaneously differentiate into spheroidal aggregates, also referred to as embryoid bodies (EBs). The identification of growth factors playing a decisive role in cardiogenesis is a crucial issue for the generation of mature cardiomyocytes. Methods: In order to identify growth factors promoting cardiac development, we established a new differentiation protocol using a defined serum-replacement medium (SRM) containing 5µg/ml insulin and 5µg/ml transferrin in combination with Dulbecco’s Modified Eagle Medium (DMEM). Furthermore, we added platelet-derived growth factor-BB (PDGF-BB) or sphingosine-1-phosphate (SPP) to promote cardiac differentiation. Results: Using SRM/DMEM, we obtained a 6-fold increase of cardiac specific myosin heavy chain α and β (cMHCα/β) in relation to 0,2% foetal calf serum (FCS)/DMEM (= 100%). Stimulation of EBs with PDGF-BB in the presence of SRM/DMEM resulted in a further 2,6-fold enhancement in comparison with the SRM/DMEM-induced increase of cMHCα/β (= 100%). A parallel increase in the number of beating EBs was observed. Similar results were obtained after stimulation of EBs with 5µg/ml SPP. Conclusion: We established a serum-free protocol and identify PDGF-BB and SPP as potent factors promoting cardiogenesis in ES cells.