In vivo reprogramming towards pluripotency for tissue repair and regeneration

The generation of pluripotent-like, proliferative cells within an injured, aged or degenerated tissue via direct in vivo reprogramming (OSKM overexpression) has been proposed as a new therapeutic avenue to tackle conditions in which the regenerative capabilities of the organism cannot cope with the magnitude of cell loss. Thanks to their capacity to proliferative and to re-differentiate into mature phenotypes, in vivo reprogrammed cells could act as an in situ source of replacement cells, avoiding the challenges associated to ex vivo cell therapy. In this Chapter, we discuss this and other opportunities offered by the in vivo overexpression of reprogramming factors (OSKM) and analyse the challenges ahead of the clinical translation of this strategy. Encouraging, yet scarce, studies that confirm enhanced regeneration following in vivo OSKM overexpression in different models of tissue injury are also discussed, with special focus on induction schemes specifically designed to avoid tumorigenesis.