Weak magnetic fields alter stem cell-mediated growth.

Biological systems are constantly exposed to electromagnetic fields (EMFs) in the form of natural geomagnetic fields and EMFs emitted from technology. While strong magnetic fields are known to change chemical reaction rates and free radical concentrations, the debate remains about whether static weak magnetic fields (WMFs; <1 mT) also produce biological effects. Using the planarian regeneration model, we show that WMFs altered stem cell proliferation and subsequent differentiation via changes in reactive oxygen species (ROS) accumulation and downstream heat shock protein 70 (Hsp70) expression. These data reveal that on the basis of field strength, WMF exposure can increase or decrease new tissue formation in vivo, suggesting WMFs as a potential therapeutic tool to manipulate mitotic activity.

Staying in shape: Planarians as a model for understanding regenerative morphology.

A key requirement of tissue/organ regeneration is the ability to induce appropriate shape in situ. Regenerated structures need to be integrated with pre-existing ones, through the combined regulation of new tissue growth and the scaling of surrounding tissues. This requires a tightly coordinated control of individual cell functions such as proliferation and stem cell differentiation. While great strides have been made in elucidating cell growth and differentiation mechanisms, how overall shape is generated during regeneration remains unknown. This is because a significant gap remains in our understanding of how cell behaviors are coordinated at the level of tissues and organs. The highly regenerative planarian flatworm has emerged as an important model for defining and understanding regenerative shape mechanisms. This review provides an overview of the main processes known to regulate tissue and animal shape during planarian regeneration: adult stem cell regulation, the reestablishment of body axes, tissue remodeling in pre-existing structures, organ scaling and the maintenance of body proportion, and the bioelectrical regulation of animal morphology. In order for the field to move forward, it will be necessary to identify shape mutants as a means to uncover the molecular mechanisms that synchronize all these separate processes to produce the worm's final regenerative shape. This knowledge will also aid efforts to define the mechanisms that control the termination of regenerative processes.

Methylisothiazolinone toxicity and inhibition of wound healing and regeneration in planaria.

Methylisothiazolinone (MIT) is a common biocide used in cosmetic and industrial settings. Studies have demonstrated that MIT is a human sensitizer, to the extent that in 2013 MIT was named allergen of the year. Recently, we showed that MIT exposure in Xenopus laevis (the African clawed frog) inhibits wound healing and tail regeneration. However, it is unknown whether MIT affects these processes in other animals. Here, we investigated the effects of MIT exposure in planaria-non-parasitic freshwater flatworms able to regenerate all tissues after injury. Using a common research strain of Dugesia japonica, we determined that intact planarians exposed to 15µM MIT displayed both neuromuscular and epithelial-integrity defects. Furthermore, regenerating (head and tail) fragments exposed to 15µM MIT failed to close wounds or had significantly delayed wound healing. Planarian wounds normally close within 1h after injury. However, most MIT-exposed animals retained open wounds at 24h and subsequently died, and those few animals that were able to undergo delayed wound healing without dying exhibited abnormal regeneration. For instance, head regeneration was severely delayed or inhibited, with anterior structures such as eyes failing to form in newly produced tissues. These data suggest that MIT directly affects both wound healing and regeneration in planarians. Next, we investigated the ability of thiol-containing antioxidants to rescue planarian wound closure during MIT exposure. The data reveal both n-acetyl cysteine and glutathione were each able to fully rescue MIT inhibition of wound healing. Lastly, we established MIT toxicity levels by determining the LC50 of 5 different planarian species: D. japonica, Schmidtea mediterranea, Girardia tigrina, Girardia dorotocephala, and Phagocata gracilis. Our LC50 data revealed that concentrations as low as 39µM (4.5ppm) are lethal to planarians, with concentrations of just 5µM inhibiting wound healing, and suggest that phylogeny is predictive of species toxicity levels. Together these results indicate MIT may have broad wound healing effects on aquatic species in general and are not limited to X. laevis alone. Future studies should investigate the impact of MIT on wound healing in other organisms, including non-aquatic organisms and mammals.