Restoration of DNA integrity and the cell cycle by electric stimulation in planarian tissues damaged by ionizing radiation

Abstract

Exposure to high levels of ionizing γ-radiation leads to irreversible DNA damage and cell death. Here, we establish that exogenous application of electric stimulation enables cellular plasticity to reestablish stem cell activity in tissues damaged by ionizing radiation. We show that sub-threshold direct current stimulation (DCS) rapidly restores pluripotent stem cell populations previously eliminated by lethally γ-irradiated tissues of the planarian flatworm Schmidtea mediterranea. Our findings reveal that DCS enhances DNA repair, transcriptional activity, and cell cycle entry in post-mitotic cells. These responses involve rapid increases in cytosolic [Ca2+] through the activation of L-type Cav channels and intracellular Ca2+ stores leading to the activation of immediate early genes and ectopic expression of stem cell markers in postmitotic cells. Overall, we show the potential of electric current stimulation to reverse the damaging effects of high dose γ-radiation in adult tissues. Furthermore, our results provide mechanistic insights describing how electric stimulation effectively translates into molecular responses capable of regulating fundamental cellular functions without the need for genetic or pharmacological intervention.

A Comprehensive conceptual and computational dynamics framework for autonomous regeneration of form and function in biological organisms

“…Another promising aspect that could be incorporated into our framework is electrophysiological stimulation in repair and regeneration. Amazing results have been reported on the activation of regeneration in immobilized and irradiated planaria through direct current stimulation (DCS), which restored stem cell features that had been eliminated by radiation ( 41 ). This was accompanied by reactivation of cell cycle gene expression and DNA-damage repair response in lethally irradiated tissues.…”

Cell quiescence in planarian stem cells, interplay between p53 and nutritional stimuli

“…Evolution does not take missteps and since the state of quiescence of the DMC cells is firmly maintained, they should constitute an advantage for D. japonica . A very audacious speculation about a putative function for these cells came from the reading of the unpublished pre-print of Davidian et al [55] in which they demonstrate the ability of electric stimulation to reverse damaging effects of high dose X-rays inducing ectopic expression of stem cell markers in post-mitotic cells. However, this phenomenon is only observable when in the irradiated host is grafted a small piece of tissue from a donor containing neoblasts.…”

Microtubule-associated protein 1B is implicated in stem cell commitment and nervous system regeneration in planarians

“…At the end of the cycle, in the case of asymmetric division, a newly produced neoblast could reenter the cell cycle and specialize towards a different cell fate suggesting that a specialized neoblast could reacquire pluripotency [ 5 ]. Additional evidence in support of such plasticity have been recently provided [ 6 , 7 ].…”