In vivo reprogramming for tissue regeneration and organismal rejuvenation

Human Pluripotent Stem Cell-Derived Tumor Model Uncovers the Embryonic Stem Cell Signature as a Key Driver in Atypical Teratoid/Rhabdoid Tumor

“…Takahashi and Yamanaka (2006) succeeded to confer ESC properties to somatic cells upon the transient expression of four reprogramming factors. Recently, an in vivo reprogramming strategy, which enables the fate conversion of differentiated somatic cells to pluripotent stem cells (PSCs) in vivo, has been developed (Taguchi and Yamada, 2017). Notably, a premature termination of the in vivo reprogramming in mice causes the development of pediatric cancer-like tumors with activation of the ESC-like signature (Ohnishi et al, 2014).…”

From Cancer to Rejuvenation: Incomplete Regeneration as the Missing Link (Part II: Rejuvenation circle)

“…Cells of the second type are cells of precancerous tissues that, through spontaneous reprogramming (via the same regulators, Notch, Wnt, Hedgehog, OSKM and others), can reverse aging, but, at the same time, cause cancer [ 6 , 7 ]. It should be noted that the same happens as the result of using main cancer treatment methods (chemotherapy, antiangiogenic therapy, radio- and immunotherapy), wherein senescence and death of tumor cells give rise to a spontaneous de novo wave of reprogramming with the return of resistant forms of cancer [ 6 ], and for all types of induced reprogramming for rejuvenation purposes [ 8 , 9 ].…”

Bench to bedside: Current advances in regenerative medicine

“…An alternative in situ approach for regenerative medicine is reprogramming of terminally differentiated cells. One current strategy for in vivo reprogramming involves enforcing expression of key regulatory transcription factors (TFs) to convert cells to an alternative mature state [6]. This strategy can be employed to generate functional cells to replace those lost through disease.…”

“…This has driven the development of many next-generation regenerative strategies. The new approaches include methods to promote endogenous tissue repair, through the use of pharmacological bio-scaffolds [5], in vivo cell reprogramming [6], and senolytics [7], methods to produce novel autologous cell therapies using induced pluripotent stem cells (iPSCs) [8]*, and techniques aimed at engineering functional human tissues and organs through in vitro tissue engineering [9]** and interspecies chimerism [10]**. In this review we will focus on these emerging strategies in the field of regenerative medicine and discuss the technical and translational challenges they pose.…”