Embryonic stem cells and the problem of directed differentiation

During the last two decades molecular genetic and cell mechanisms of proliferation and differentiation of mammalian stem cells have been intensively studied in leading laboratories all over the world. Studies in this field are very important both for basic science and for the development of promising cell therapy technologies. Embryonic stem cells represent a unique experimental model for the investigation of basic principles of mammalian cell differentiation and development. Using this model, important data on similarity in genetic programs during embryonic development and embryonic stem cells differentiation have been obtained. These include basically similar consequent expression of transcription factors, cell receptors, tissue specific proteins, and ion channels. Lines of embryonic stem cells are widely used for the investigation of gene functions in ontogenesis as well as in adult organisms (using gene-knockout strategy). This review deals with different pathways of mammalian (including human) embryonic stem cells differentiation. It considers the main approaches to directed differentiation of these cells in vitro: use of feeder cells, growth factors, and other chemical compounds and also genetic modification. Some examples of application of embryonic stem cells derivatives for cell therapy of some pathological conditions are discussed.