Reactive Oxygen Species and Weak Magnetic Fields: Unraveling the Mechanisms of Planarian Regeneration and Tissue Growth
Date of Award
Doctor of Philosophy
Wendy S. Beane, Ph.D.
John Jellies, Ph.D.
Jeremy Duncan, Ph.D.
Labib Rouhana, Ph.D.
Planaria, reactive oxygen species, regeneration, ROS, weak magnetic fields, WMF
Reactive oxygen species (ROS) play a critical role in basic cellular behaviors such as apoptosis, proliferation, and differentiation. These molecules once thought to be harmful byproducts of metabolism, are also required for many complex and ubiquitous processes like wound healing, development, and regeneration. This study investigates the influence of ROS on planarian regeneration, with a particular focus on ROS dynamics in stem cell-mediated tissue growth. Data reveal that modulation of ROS levels leads to changes in cellular behaviors and tissue growth outcomes. Inhibition of ROS accumulation blocks stem cell proliferation and tissue growth, preventing planarian regeneration, while partial ROS accumulation stunts growth. Promoting ROS accumulation above endogenous levels promotes additional stem cell proliferation, yielding an increase in tissue formation. This study also details how exposure to weak magnetic fields (WMFs) alters these regenerative outcomes by modulating injury-induced ROS levels in a field-strength-dependent manner. These data support a theoretical basis for WMF effects on biological systems, built upon spin state theory and the radical pair mechanism. This theoretical model was used to formulate and test predictions on whether WMFs could influence ROS-dependent events like regeneration. These data demonstrate that exposure to a 200 T WMF decreased ROS levels and inhibited subsequent stem cell division and growth. Conversely, exposure to a 500 T WMF increased ROS levels, resulting in greater stem cell division and tissue growth. These data highlight the reciprocal ability of WMFs to influence regeneration. Furthermore, this work identifies the need for future investigations to elucidate the contributions of distinct ROS and their in vivo production methods. For example, hydrogen peroxide and superoxide both accumulate at the wound site in response to injury. However, initial data suggest that WMF effects are due to changes in superoxide levels. In addition, determining whether specific ROS were generated by the mitochondria or cytosolic proteins could unravel the intricate mechanisms underlying stem cell behaviors and regeneration. Integrating these findings into a comprehensive framework offers insights into the context-dependent effects of ROS. Thus, understanding how WMFs could be used to target certain cell behaviors may provide a foundation for novel innovations in cancer therapeutics and regenerative medicine.
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Kinsey, Luke James, "Reactive Oxygen Species and Weak Magnetic Fields: Unraveling the Mechanisms of Planarian Regeneration and Tissue Growth" (2023). Dissertations. 4013.