Transient transcription factor (OSKM) expression is key towards clinical translation of in vivo cell reprogramming

• Published in: EMBO molecular medicine Vol. 9; no. 6; pp. 733 - 736
• Main Authors: de Lázaro, Irene, Cossu, Giulio, Kostarelos, Kostas
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.06.2017; John Wiley & Sons, Inc; EMBO Press; John Wiley and Sons Inc; Springer Nature
• Subjects: Adult; c-Myc protein; Cell Differentiation; Cellular Reprogramming; Commentaries; Commentary; EMBO34; EMBO39; Gene Expression Regulation; Humans; KLF4 protein; Myc protein; Oct-4 protein; Octamer Transcription Factor-3 - genetics; Pluripotency; Regenerative medicine; SOXB1 Transcription Factors - genetics; Tissue engineering; Transcription Factors; Translation; Tumorigenesis
• DOI: 10.15252/emmm.201707650
• ISSN: 1757-4676

Reprogramming adult, fully differentiated cells to pluripotency in vivo via Oct3/4 , Sox2 , Klf4 and c‐Myc (OSKM) overexpression has proved feasible in various independent studies and could be used to induce tissue regeneration owing to the proliferative capacity and differentiation potential of the reprogrammed cells. However, a number of these reports have described the generation of teratomas caused by sustained reprogramming, which precludes the therapeutic translation of this technology. A recent study by the Izpisúa‐Belmonte laboratory described a cyclic regime for short‐term OSKM expression in vivo that prevents complete reprogramming to the pluripotent state as well as tumorigenesis. We comment here on this and other studies that provide evidence that in vivo OSKM induction can enhance tissue regeneration, while avoiding the feared formation of teratomas. These results could inspire more research to explore the potential of in vivo reprogramming in regenerative medicine. Graphical Abstract de Lázaro, Cossu and Kostarelos comment on the prospects of short‐term in vivo OSKM induction to initiate cell reprogramming and enhance tissue regeneration, while avoiding the threat of generating teratomas.