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Mechanisms from Non-Mammalian Species Used to Regrow Sensory Hair Cells in Mice

Many other species are more regenerative than we are, and mammals in general are less regenerative than is the case for some other clades. It is too early to say whether ongoing investigations of the basis for proficient regeneration will lead to ways to safely adjust our biochemistry to perform greater feats of healing. Even simple mechanisms, if found, may be turn out to be very hard to introduce into humans. Everything in cellular biochemistry is connected to everything else; nothing can be changed in isolation. The greatest hope is that mechanisms of regeneration that are active in other species are merely dormant in mammals, but again it is too early to say with any confidence as to whether or not this is the case, despite promising signs in recent years.

Hearing impairment has long been accepted as a fact of life for the aging population - an estimated 30 million Americans suffer from some degree of hearing loss. However, scientists have long observed that other animals - namely birds, frogs, and fish - have been shown to have the ability to regenerate lost sensory hair cells. "It's funny, but mammals are the oddballs in the animal kingdom when it comes to cochlear regeneration. We're the only vertebrates that can't do it."

In 2012 researchers identified a family of receptors - called epidermal growth factor (EGF) - responsible for activating support cells in the auditory organs of birds. When triggered, these cells proliferate and foster the generation of new sensory hair cells. The researchers speculated that this signaling pathway could potentially be manipulated to produce a similar result in mammals. "In mice, the cochlea expresses EGF receptors throughout the animal's life, but they apparently never drive regeneration of hair cells. Perhaps during mammalian evolution, there have been changes in the expression of intracellular regulators of EGF receptor family signaling. Those regulators could have altered the outcome of signaling, blocking regeneration. Our research is focused on finding a way switch the pathway temporarily, in order to promote both regeneration of hair cells and their integration with nerve cells, both of which are critical for hearing."

In a new study, researchers tested the theory that signaling from the EGF family of receptors could play a role in cochlear regeneration in mammals. The researchers focused on a specific receptor called ERBB2 which is found in cochlear support cells. One set of experiments involved using a virus to target ERBB2 receptors. Another involved mice genetically modified to overexpress an activated ERBB2. A third experiment involved testing two drugs, originally developed to stimulate stem cell activity in the eyes and pancreas, that are known activate ERBB2 signaling. The researchers found that activating the ERBB2 pathway triggered a cascading series of cellular events by which cochlear support cells began to proliferate and start the process of activating other neighboring stem cells to become new sensory hair cells. Furthermore, it appears that this process not only could impact the regeneration of sensory hair cells, but also support their integration with nerve cells.

Link: https://www.urmc.rochester.edu/news/story/5448/study-points-to-possible-new-therapy-for-hearing-loss.aspx

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