Induction of pluripotent stem cells from adult somatic cells by protein-based reprogramming without genetic manipulation. Blood. 2010 May 3; Authors: Cho HJ, Lee CS, Kwon YW, Paek JS, Lee SH, Hur J, Lee EJ, Roh TY, Chu IS, Leem SH, Kim Y, Kang HJ, Park YB, Kim HS The concept of reprogramming of somatic cells has opened a new era in regenerative medicine. Transduction of defined factors has successfully achieved pluripotency. However, during the generation process of induced pluripotent stem (iPS) cells, genetic manipulation of certain factors may cause tumorigenicity, which limits further application. We report that that a single transfer of ESC (embryonic stem cell)-derived proteins into primarily cultured adult mouse fibroblasts, rather than repeated transfer or prolonged exposure to materials, can achieve full reprogramming up to the pluripot! ent state without the forced expression of ectopic transgenes. During the process, gene expression and epigenetic status were converted from somatic to ES-equivalent status. We verified that protein-based reprogramming was neither by the contamination of protein donor ESC nor by DNAs/RNAs from donor ESC. Protein-iPS cells were biologically and functionally very similar to ES cells and differentiated into 3-germ layers in vitro. Furthermore, Protein-iPS cells possessed in vivo differentiation (well-differentiated teratoma formation) and development (chimeric mice generation and a tetraploid blastocyst complementation) potentials. Our results provide an alternative and safe strategy for the reprogramming of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy. PMID: 20439621 [PubMed - as supplied by publisher] |
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