Induction of pluripotent stem cells from adult somatic cells by protein-based dedifferentiation

The concept of dedifferentiation of somatic cells into pluripotent stem cells has opened a new era in regenerative medicine. Viral transduction of defined factors has successfully achieved pluripotency derived from somatic cells. However, during the generation process of induced pluripotent stem (iPS) cells, genetic integration of certain factors may cause mutagenesis or tumorigenicity, which limits further application. Therefore, there is currently ongoing an extensive search for new methods such as transient gene delivery and oocyte-free and non-viral inducers like small molecules. Here we show that the transient delivery of embryonic stem (ES) cell-derived soluble proteins enables dedifferentiation of mouse adult somatic cells converting them into pluripotent stem cells without the introduction of certain transcription factors or genetic manipulation. During the dedifferentiation, global gene expression patterns and epigenetic status were converted from the somatic to the ES-equivalent status. Dedifferentiated somatic cells were morphologically, biologically and functionally indistinguishable from ES cells. Furthermore, the dedifferentiated cells possessed in vivo differentiation and development potential. Our results provide an alternative and safe strategy for dedifferentiation of somatic cells that can be used to facilitate pluripotent stem cell-based cell therapy.

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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