Reversine-treated fibroblasts acquire myogenic competence in vitro and in regenerating skeletal muscle

Abstract

Stem cells hold a great potential for the regeneration of damaged tissues in cardiovascular or musculoskeletal diseases. Unfortunately, problems such as limited availability, control of cell fate, and allograft rejection need to be addressed before therapeutic applications may become feasible. Generation of multipotent progenitors from adult differentiated cells could be a very attractive alternative to the limited in vitro self-renewal of several types of stem cells. In this direction, a recently synthesized unnatural purine, named reversine, has been proposed to induce reversion of adult cells to a multipotent state, which could be then converted into other cell types under appropriate stimuli. Our study suggests that reversine treatment transforms primary murine and human dermal fibroblasts into myogenic-competent cells both in vitro and in vivo. Moreover, this is the first study to demonstrate that plasticity changes arise in primary mouse and human cells following reversine exposure.

Mechanisms of urodele limb regeneration

“…Myoseverin disrupted microtubules and upregulated genes for growth factors, immunomodulatory molecules, ECM remodeling proteases, and stress‐response genes, consistent with the activation of pathways involved in wound healing and regeneration, but did not activate the whole program of myogenic dedifferentiation in newt limbs (Duckmanton, Kumar, Chang, & Brockes, 2005). Reversine treatment of mouse C2C12 myotubes resulted in mononucleate cells that mimic mesenchymal stem cells in their ability to differentiate in vitro into osteoblasts and adipocytes, as well as muscle cells (Anastasia et al., 2006). Myoseverin and reversine are thus useful in analyzing the events of structural remodeling involved in dedifferentiation and may have natural counterparts that can be isolated.…”

Looking proximally and distally: 100 years of limb regeneration and beyond

“…Another synthetic small molecule isolated by a chemical library screen, a disubstituted purine dubbed reversine, can induce the dedifferentiation of some cell types. Reversine treatment of C2C12 myoblasts resulted in mononucleate cells that behaved like mesenchymal stem cells (MSCs); i.e., they were able to differentate in vitro into osteoblasts and adipocytes, as well as muscle cells (Anastasia et al, 2006). Myoseverin and reversine may be useful in analyzing the events of structural remodeling.…”

Stretching the limits: Stem cells in regeneration science

“…This process involves growth arrest by activation of the PI3K pathway and enhancement of Polycomb gene expression, suggesting that the mechanisms of differentiation gene silencing in ESCs and ASCs may be partly similar. Reversine-treated mouse dermal fibroblasts have been shown to participate in muscle regeneration when injected into the injured tibialis anterior muscle (Anastasia et al, 2006). Finally, retinoic acid is a small natural molecule involved in many aspects of cell differentiation.…”