The Quest to Derive Keratinocytes from Pluripotent Stem Cells
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PLURIPOTENTIAL STEM CELLS (WE LOWRY, SECTION EDITOR)
The Quest to Derive Keratinocytes from Pluripotent Stem Cells James G. Rheinwald
Published online: 31 March 2013 Springer Science+Business Media New York 2013
Abstract The derivation of keratinocytes from pluripotent stem cells (PSCs) is a worthy goal. Epidermal and corneal keratinocytes cultured from normal human tissue have been very well-characterized for their growth and differentiation properties and their ability to regenerate permanent tissue as autologous transplants. PSC-derived keratinocytes would therefore be ideal for establishing proof-of-principle that normal, well-defined, and functional somatic cell types can be derived from PSCs and used successfully in tissue replacement therapies. Much progress has been made to identify experimental protocols for deriving cells that display some keratinocyte properties from ES and iPS cells. However, the proliferative potential of these cells typically is very limited and many features of these cells are common to all members of the large family of p63 epithelial cell types. Thus many lines of investigation remain to be examined more thoroughly in this important and exciting field. Keywords Epithelial p63 Embryonic Ectoderm Cultured cells Keratin
Introduction The cultivation of pluripotent embryonic stem (ES) cell lines from mice [1, 2] became the basis for gene knockout technology, which supports much of current experimental
J. G. Rheinwald (&) Department of Dermatology and Harvard Skin Disease Research Center, Brigham and Women’s Hospital and Harvard Medical School, HIM 664, 77 Ave. Louis Pasteur, Boston, MA 02115, USA e-mail: [email protected]
biology. Generation of similar cell lines from human embryos [3, 4] engendered interest in the idea of inducing these cells to differentiate in culture into clinically useful adult somatic cell types, especially those that are postmitotic in the adult and may deteriorate or become damaged, resulting in severe pathologies. With the discovery that transient expression of four factors can reprogram somatic cells such as skin fibroblasts to a pluripotent state similar to that of ES cells [5–8] (‘‘induced pluripotent stem (iPS) cells’’ came the prospect of producing autologous somatic cell types from iPS cells for therapeutic transplantation [9]. The subject of this review is research aimed at producing epidermal and corneal keratinocytes from ES and iPS cells. There is no pressing clinical need for PSC-derived keratinocytes, since autologous tissue-derived keratinocytes can be expanded rapidly in culture and transplanted to provide permanent epidermal coverage of full-thickness burn wounds [10, 11] and corneal restoration in cases of chemical damage to the eye surface [12]. However, more is known about the keratinocyte than any other cultivable cell type, with respect to growth regulation, protein expression, differentiation, and methods of transplantation to regenerate permanent tissue. It therefore is the ideal cell type for proofof-principle that au
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