A groundbreaking study has revealed that an injury to one region of the body can activate a healing response in another part of the organism. The research, led by Bo Wang, an assistant professor of bioengineering at Stanford, shows that this whole-body synchronisation is crucial for wound healing and tissue regeneration in planarian worms.
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Planarian worms, small flatworms measuring half an inch, possess an extraordinary ability to regenerate in almost any situation. If a planarian is cut into four parts, each part can regenerate into a new flatworm in just a few days. Interestingly, wounds in one part of a planarian's body appear to trigger reactions in distant tissues, a phenomenon observed in mice, zebrafish, and axolotls as well.
Bo Wang sought to understand how these responses were coordinated, and one possible mechanism was the extracellular signal-related kinase (ERK) pathway. Cells use the ERK pathway to communicate with each other, sending signals out in a wave-like manner. When tissue is injured, nearby cells pass on that information to their neighboring cells, creating a propagation of signals throughout the organism.
However, there was a problem: past research showed that ERK waves moved too slowly to be of any use. "If I propagate a signal at 10 microns per hour, it can take days to go through one millimeter," Wang explained. This speed was far too slow to aid in wound healing and regeneration in planarians.
To their surprise, the researchers discovered that ERK waves traveled over 100 times faster than previously observed. Instead of traveling in small steps from cell to cell, the waves moved along extra-long body-wall muscle cells, acting as "superhighways," which accelerated the signal from one end of the body to another in hours instead of days.
The researchers then conducted an experiment to determine if the entire body was involved in the healing response. By cutting off a planarian's head, they found that the head regrows quickly from the remaining body after decapitation. However, when they blocked the ERK signal from spreading to the back half of the organism, the head didn't just heal slower; it never regrew at all.
Further experiments showed that the regeneration process could be "rescued" by removing the planarian's tail as well. This alerted the tail tissue of the injury, and astonishingly, both the tail and the head regrew.
The study's findings have implications for human healing and regeneration. While animals like planarians, sea stars, and axolotls exhibit extraordinary regenerative abilities, humans lack such capabilities. Understanding why this is the case could lead to advancements in medical treatments and interventions, including those related to cancer.
Wang emphasized that tissues in a wounded state all the time could potentially lead to cancer, so regeneration is usually turned "off" until the entire body agrees that it's time to turn "on." The researchers also noted that hundreds of genes were turned on and off as ERK waves spread throughout planarians' bodies, and although humans are distantly related to planarians, they share many of the same genes. This opens up avenues for exploring these genes and understanding how animals regenerate while managing the risk of uncontrolled cancerous growth.
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