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New research challenges approach to regeneration in human medicine

Posting time:2022-12-06 00:19:32

New research challenges approach to regeneration in human medicine

New findings suggest a changing perspective on how regeneration is done in human medicine. Ken Muneoka has a history of shaking up the field of regeneration; as in a breakthrough article published in Nature in 2019, the Texas A&M University College of Veterinary and Biomedical Sciences (CVMBS) professor demonstrated for the first time breastfeeding Possibility of animal joint regeneration. Already, his team is further questioning long-held notions of basic science on the subject, this time about how mammals might regenerate damaged parts of their bodies. Only some organs like the liver and certain tissues like the epidermis, the top layer of the skin can regenerate naturally in humans. Other species -- most notably salamanders -- have the ability to regenerate complex parts, including bones, joints and even entire limbs. So, for more than 200 years, researchers have been studying these animals and trying to understand the processes behind limb regeneration, with the hope of one day translating these principles into triggering a more comprehensive regenerative capacity in humans. Thanks to this research, it is now widely believed that the presence of nerves is the single most important factor in limb regeneration. While this may be true for salamanders and other species, it's not true for mammals, according to two recent studies by Muneoka. The first study, published in the Journal of Bone and Mineral Research in 2021, demonstrates the ability of mammals to require mechanical loading or exert force on the affected location. The second study, recently published in Developmental Biology, demonstrated that regeneration is not hindered by a lack of nerves. Taken together, these findings represent a dramatic shift in thinking about regeneration in human medicine. "These two studies show two centuries of dogma that you need nerves to regenerate. What replaced it in mammals is that you need mechanical loads, not nerves," Muneoka said. The importance of mechanical loads Scientists It has long been thought that in order to induce regeneration in mammals, two things must be present in the affected area. The first is growth factors, which are molecules that stimulate cells to regrow and rebuild body parts. In natural regeneration, these growth factors are produced by the body and they vary by species and area of ​​regeneration. For human-induced regeneration, these growth factors must be introduced into the region. The second factor considered necessary is nerves. The premise of this belief is that the area where many previous studies of human-induced mammalian regeneration have been done is usually the fingertip, and the entire limb can no longer be used without nerves. These studies would have predicted results - regeneration did not occur when growth factors were introduced, leading to the conclusion that, like other species, nerves are a requirement for regeneration. However, the mechanical load aspect is ignored. In their study, Muneoka and colleagues decided to take a step back and asked the question -- "Is it really the nerve, or is the lack of mechanical loading also part of the equation?" Connor Dolan, lead author of the paper on two new studies, thinks developed a method to test denervation requirements in mammals inspired by astronauts. The technique, known as hindlimb suspension, has been used by NASA and other scientists for decades to test how mammals respond to zero-gravity environments. A similar procedure is used in the medical procedure of the legs of large animals to prevent the animal from putting weight on the affected limb. "Dolan found that when the limb is dangling, although they still have a lot of nerves to move around, they can't actually put pressure on the limb, so the fingertip doesn't regenerate," Muneoka said. "It just completely inhibits regeneration. "However, once the mechanical load was restored, regeneration was rescued. "Absolutely nothing happens during the pause," Muneoka said, "but once the load returns there will be a delay of a few weeks, but then they will start to regenerate." This first step demonstrates that even though nerves may be required, mechanical Load is a critical component of regeneration. Building on the research, Dolan's second paper shows that if a mouse has no nerves in one finger but has nerves in the other fingers, it is still applying force to the disabled finger and the finger will still regenerate, which Shows that nerves are not needed. "He found that they regenerated a little bit slowly, but they regenerated perfectly normally," Muneoka said. Implications of the study Muneoka is quick to point out, though, that their study isn't to say that previous research is wrong, just that it doesn't directly apply to humans. "There's been a lot of research in salamanders that they don't regenerate when you remove nerves," Muneoka said. "Researchers have also been able to put growth factors that they know are produced by nerves into cells and rescue regeneration. So, Salamanders may indeed need nerves to regenerate, but if we're going to regenerate limbs in humans, it's going to be more like what happens in mice." Some of Muneoka's ideas since he first started studying regeneration more than 20 years ago have The generally accepted theory of regeneration has fought back. He said it took almost three years to get the two papers published because they initially tried to submit them together. Future Road Mammalian regeneration does not require nerves, which seems to be an academic question. After all, what's the point of regenerating a limb if a person can't feel it or control it because it doesn't have nerves? In this sense, nerves will remain an important piece of the puzzle. From Muneoka's perspective, the shift is that rather than thinking of nerves as a requirement for regeneration, they think of nerves as part of the need for regeneration. The problem, says Larry Suva, director of the Department of Veterinary Physiology and Pharmacology (VTPP) at CVMBS, is that no one has even considered the load aspect before. "Think of a blast wound, a soldier left with a stump. Before this paper, no one was even thinking about the requirement of mechanical effects. You're showing people that a transgender animal doesn't regenerate, and they think it It's because the nerve is cut, but no one studies the mechanical load side." As Suva points out, science is full of people looking for the best places for light. "I work on bones, so when I see a problem, I'm looking at a bone problem. People who work on nerves, they're looking at nerves. So people like Dr. Muneoka are very rare and they take a step back , to take a more holistic view. That's what he brings to this idea, to this 200-year-old data. We now have to look at regeneration through a different lens because now we know that mechanical effects are extremely important," Suva said. One of the results of the nerve-focused research is that scientists have been able to recreate the growth factors that nerves produce, allowing researchers to start regeneration in salamanders even when nerves are not present. With these new findings, Suva noted, scientists will now know that if they want to start regeneration in mammals then they have to do the same with mechanical loading. This is because cells respond differently to mechanical loading, which is somehow translated into biochemistry inside the cell. "There are a handful of labs working on the biochemical underpinnings of the effects of mechanical loading on cells," Muneoka said. "If we can understand this biochemical signal, then maybe the physical force of mechanical loading can be replaced by some kind of cocktail of molecules that is The end of the road to full human regeneration may still be far in the future, but Suva points out that this fundamental shift in thinking is an important sign on that path. "Regeneration of human limbs may still be science fiction, but we know some facts about it, and now we know that you have to have this mechanical load and growth factors. This changes the way scientists and engineers of the future are going to solve this problem. In making There are still many complex questions that need to be addressed before whole human limb regeneration is possible, but Dr. Muneoka's discovery is an important next step in ensuring we address the right questions."

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