Epigenetic dedifferentiation of somatic cells into pluripotency: cellular alchemy in the age of regenerative medicine?
Ever since the derivation of the first human embryonic stem cell line, hopes have persisted for the treatment of a wide range of cellular degenerative diseases. However, significant immuno-incompatibility between donor cells and recipient patients remains an unsolved challenge. Currently, three main strategies are investigated in humans to create autologous pluripotent stem cells: somatic cell nuclear transfer, cell fusion and cell extract incubation. All methods exploit the fact that a somatic genome is amenable to epigenetic dedifferentiation into a more plastic state, presumably through direct exposure to and manipulation by heterologous transcriptional factors. Epigenetic reprogramming includes profound modifications of chromatin structure, but the responsible mechanisms that work in toti- and pluripotent cells remain largely unknown. This review presents a brief introduction to stem cell terminology and epigenetics, followed by a critical examination of the predominant methodologies involved. Finally, the search for specific reprogramming factors is discussed, and obstacles for the clinical implementation of reprogrammed cells are addressed.
Oliveri
Roberto S
RS
The Juliane Marie Center for Children, Women, and Reproduction, Laboratory of Reproductive Biology, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. oliveri@rh.dk
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002459:Cell Fusion; D065150:Cellular Reprogramming; D044127:Epigenesis, Genetic; D005544:Forecasting; D006801:Humans; D008954:Models, Biological; D053652:Nuclear Transfer Techniques; D039904:Pluripotent Stem Cells / Q000166:cytology*; D044968:Regenerative Medicine