Clonal stem cell biology

Jose Cibelli

Advanced Cell Technology Worcester, Massachusetts USA

It was 1982 when the first pluripotent stem cells were described but it wasnt until 1998 when these cells entered the main arena of medical and scientific research. Since then, stem cells turned into the focus of attention of scientists, physicians, lawmakers and the public at large. There reason is simple, these cells may be the solution for many devastating human diseases that today have no cure. Stem cells have intrinsic properties that make them highly desirable, they can divide indefinitely and when stimulated by differentiation factors they can give raise to several, more differentiated cell types. One of the most fascinating aspects of these cells is the possibility to clonally produce them from a somatic cell. This techniques have been developed in bovine1 in our laboratory, and studies in mice later confirmed our findings 1-3. Since then, we have learnt that there are different types of cells within the mammalian body that can be used as nuclear donor for the generation of not only ES cells, but whole animals as well 4. We are currently attempting to de-differentiate adult human skin fibroblasts into pluripotent cells using this same approach5. This review will focus on embryonic stem cells making particular emphasis on somatic cell-derived embryonic stem cells considering their current state of development and their potential therapeutic applications. References: 1. Cibelli, J.B. et al. Transgenic bovine chimeric offspring produced from somatic cell-derived stem-like cells [see comments]. Nat Biotechnol 16, 642-646 (1998). 2. Wakayama, T. et al. Differentiation of embryonic stem cell lines generated from adult somatic cells by nuclear transfer. Science 292, 740-743. (2001). 3. Munsie, M.J. et al. Isolation of pluripotent embryonic stem cells from reprogrammed adult mouse somatic cell nuclei. Curr Biol 10, 989-992 (2000). 4. Cibelli, J.B. et al. Cloned transgenic calves produced from nonquiescent fetal fibroblasts [see comments]. Science 280, 1256-1258 (1998). 5. Cibelli, J. et al. Somatic Cell Nuclear Transfer in Humans: Pronuclear and Early Embryonic Development. e-biomed:The Journal of Regenerative Medicine 2, 25-31 (2001).

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Genetics & Therapy - 1.