Pluripotent Stem Cells – Model of Embryonic Development, Tool for Gene Targeting, and Basis of Cell Therapy

Abstract

Embryonic stem (ES) cells are pluripotent cell lines with the capacity of self-renewal and a broad differentiation plasticity. They are derived from pre-implantation embryos and can be propagated as a homogeneous, uncommitted cell population for an almost unlimited period of time without losing their pluripotency and their stable karyotype. Murine ES cells are able to reintegrate fully into embryogenesis when returned into an early embryo, even after extensive genetic manipulation. In the resulting chimeric offspring produced by blastocyst injection or morula aggregation, ES cell descendants are represented among all cell types, including functional gametes. Therefore, mouse ES cells represent an important tool for genetic engineering, in particular via homologous recombination, to introduce gene knock-outs and other precise genomic modifications into the mouse germ line. Because of these properties ES cell technology is of high interest for other model organisms and for livestock species like cattle and pigs. However, in spite of tremendous research activities, no proven ES cells colonizing the germ line have yet been established for vertebrate species other than the mouse (Evans and Kaufman, 1981; Martin, 1981) and chicken (Pain et al., 1996). The in vitro differentiation capacity of ES cells provides unique opportunities for experimental analysis of gene regulation and function during cell commitment and differentiation in early embryogenesis. Recently, pluripotent stem cells were established from human embryos (Thomson et al., 1998) and early fetuses (Shamblott et al., 1998), opening new scenarios both for research in human developmental biology and for medical applications, i.e. cell replacement strategies. At about the same time, research activities focused on characteristics and differentiation potential of somatic stem cells, unravelling an unexpected plasticity of these cell types. Somatic stem cells are found in differentiated tissues and can renew themselves in addition to generating the specialized cell types of the tissue from which they originate. Additional to discoveries of somatic stem cells in tissues that were previously not thought to contain these kinds of cells, they also appear to be capable of developing into cell types of other tissues, but have a reduced differentiation potential as compared to embryo-derived stem cells. Therefore, somatic stem cells are referred to as multipotent rather than pluripotent. This review summarizes characteristics of pluripotent stem cells in the mouse and in selected livestock species, explains their use for genetic engineering and basic research on embryonic development, and evaluates their potential for cell therapy as compared to somatic stem cells.

Sodium butyrate and dexamethasone promote exocrine pancreatic gene expression in mouse embryonic stem cells

“…Mouse embryonic stem (ES) cells are isolated from the inner cell mass of blastocysts, which are capable of indefinite and pluripotential proliferation [1,2] . Certain differentiation factors involved in embryonic development can differentiate ES cells into cell types from all three germ layers in vitro [3][4][5] .…”

Cooperative and indispensable roles of endothelin 3 and KIT signalings in melanocyte development

“…In addition, neural crest cells might have been determined before delineation from the neural tube, which, therefore, would make it impossible to investigate the signals required for this process (Henion and Weston, 1997). Because of their potential to give rise to virtually all cell lineages when introduced into a blastocyst, embryonic stem (ES) cells differentiate into a variety of cell types in vitro when appropriate environmental cues are reproduced in the culture system (O'Shera, 1999;Prelle et al, 2002;Turksen, 2002;Wichterle et al, 2002;Kim et al, 2002). In these efforts, culture systems have been refined to selectively induce specific cell types and not to generate other cell types by using a combination of growth factors and forced expression of lineage-specific transcription factors.…”

Generation of structures formed by lens and retinal cells differentiating from embryonic stem cells

“…Because of their potential to give rise to virtually all cell lineages when introduced into a blastocyst, ES cells also differentiate into a variety of cell types in vitro when appropriate environmental cues are reproduced in the culture system (O'Shera, 1999;Prelle et al, 2002;Turksen, 2002;Wichterle et al, 2002;Kim et al, 2002). In these efforts, culture systems have been refined to selectively induce specific cell types and not to generate other cell types by using a combination of growth factors and forced expression of lineage-specific transcription factors.…”