Studies in mice confirm the link between mechanical and immunotherapy in muscle regeneration.
Massage has been used to treat pain and injured muscles for over 3000 years. Today, many athletes vow to rehabilitate their bodies with massage guns. But other than making people feel good, do these “mechanotherapy” actually improve healing after a serious injury? Wyss Institute for Biologically Inspired Engineering and John A at Harvard University. The answer is yes, according to a new study by researchers at the Paulson School of Engineering and Applied Sciences (SEAS).
The team used a custom-designed robot system to provide consistent and adjustable compressive force to the muscles of the mouse legs, and this mechanical load (ML) causes neutrophils from severely injured muscle tissue. We have discovered that it quickly removes immune cells called. This process also removes inflammatory cytokines released from muscle by neutrophils and enhances the process of muscle fiber regeneration.The study is published at Scientific translation medicine..
“Many people are trying to study the beneficial effects of massage and other mechanical therapies on the body, but until now it has not been done in a systematic and reproducible way. Our work is done. It shows a very clear relationship between mechanical stimulation and immune function. It promises regeneration of various tissues such as bones, tendons, hair and skin, and prevents the use of drug-based interventions. It can also be used in patients with, “said lead author Dr. Bo Ri Seo. .. I am a postdoctoral fellow in the laboratory of Dr. Dave Mooney, a core faculty member. At Wyss Institute and SEAS.
More meticulous massage gun
Seo and her co-authors began investigating the effects of mechanotherapy on injured tissue in mice a few years ago. Doubled the rate Reduced muscle regeneration and tissue scarring during 2 weeks. Excited by the idea that mechanical stimulation alone can promote regeneration and strengthen muscle function, the team explores more deeply how the process works in the body and which parameters maximize healing. Decided to understand.
They are members of the Wyss Associate Faculty, Conor Walsh, Ph.D., in collaboration with Harvard Biodesign Lab’s soft robotics experts. Led to create a small device that uses sensors and actuators to monitor and control the force exerted on the limbs of a mouse. .. “With the devices we create, we have precise control over parameters such as the amount and frequency of force applied, so we can understand tissue healing with a much more systematic approach than the manual approach,” he said. Co-author Dr. Christopher Payne said. Harvard Biodesign Lab, a former postdoctoral researcher at D., Wyss Institute, and now a robotics engineer at Viam, Inc.
When the device was ready, the team experimented with applying force to the muscles of the mouse legs through a soft silicone tip and used ultrasound to investigate what happened to the tissue accordingly. They observed that the muscles were experiencing 10-40% strain and confirmed that the tissue was experiencing mechanical forces. They also used these ultrasound image data to develop and validate computational models that could predict the amount of tissue strain under a variety of loading forces.
The injured muscle was then subjected to consistent and repetitive force for 14 days. Both treated and untreated muscles showed a decrease in the amount of damaged muscle fibers, but the decrease was more pronounced, the cross-sectional area of the fibers was greater in the treated muscles and the treatment was greater. It shows that it brought about restoration and strength recovery. It was found that the greater the force applied during treatment, the stronger the injured muscles and the better mechanotherapy improves post-injury muscle recovery. But how?
Drive out neutrophils to promote regeneration
To answer that question, scientists conducted a detailed biological assessment to analyze various inflammation-related factors called cytokines and chemokines in untreated and treated muscles. The cytokine subset was dramatically reduced in the treated muscle after 3 days of mechanical therapy. These cytokines are associated with the movement of immune cells called neutrophils, which play many roles in the inflammatory process. Treated muscles also have fewer neutrophils in the tissue than untreated muscles, suggesting that a decrease in cytokines that attract them caused a decrease in neutrophil infiltration.
The team had the premonition that the force exerted on the muscles by mechanotherapy would effectively squeeze neutrophils and cytokines from the damaged tissue. They confirmed this theory by injecting fluorescent molecules into the muscles and observing that the movement of the molecules became more important with the application of force, and supported the idea that it would help flush muscle tissue. ..
To find out how neutrophils and their associated cytokines affect muscle fiber regeneration, scientists In vitro A study in which muscle progenitor cells (MPCs) were grown in a medium in which neutrophils had previously grown. They found that the number of MPCs increased, but the rate of differentiation (developing into other cell types) decreased. This suggests that neutrophil secretory factors stimulate muscle cell growth, but the long-term presence of these factors is a new muscle fiber.
“Neutrophils are known to kill and remove pathogens and damaged tissue, but this study identified a direct effect on the behavior of muscle progenitor cells,” said a former graduate student at the Wyss Institute. Co-second author Stephanie McNamara said. Currently MD-Ph.D. A student at Harvard Medical School (HMS). “The inflammatory response is important for regeneration in the early stages of healing, but it is equally important to resolve inflammation quickly so that the regeneration process can be fully carried out.”
Then Seo and her colleague returned to them In vivo The types of muscle fibers in treated and untreated mice 14 days after injury were modeled and analyzed. They found that type IIX fibers were prevalent in healthy and treated muscles, but untreated injured muscles had a lower number of type IIX fibers and an increased number of type IIA fibers. Was there. This difference explained the increased fiber size and the production of greater force in the treated muscles, as IIX fibers generate more force than IIA fibers.
Finally, the team depleted mouse neutrophils three days after injury to ensure optimal time for neutrophils to be present in the injured muscle. The muscles of treated mice show larger fiber size and greater strength recovery than untreated mice, requiring neutrophils in the early stages of injury recovery, but removing neutrophils early from the site of injury , It was confirmed that muscle regeneration was improved.
“These findings are noteworthy because they show that they can affect the functioning of the body’s immune system in a non-invasive manner without the use of drugs,” says Paul A. of SEAS. Walsh, who is also a professor of applied science in meeder engineering, said. The group has experience in developing wearable technologies for diagnosing and treating illness. “This provides a great incentive for the development of external mechanical interventions that help accelerate and improve the healing of muscles and tissues that can be rapidly transformed into a clinic.”
The team continues to investigate this series of studies on multiple projects in the lab. They plan to test this mechanotherapy approach in larger animals with the goal of being able to test its effectiveness on humans. They also want to test for different types of injuries, age-related muscle loss, and improved muscle performance.
“Although the fields of mechanotherapy and immunotherapy rarely interact, this study considers both physical and biological factors when studying and working to improve human health. It proves how important this is, “says Robert P. Pincus Family, a professor of bioengineering in the treatise and SEAS.
“The idea that mechanics affects the functioning of cells and tissues has been ridiculed until decades. Scientists have made great strides in establishing acceptance of this fact, but the process Little is yet known about how it actually works at the organ level. This study is a previously unknown type of mechanobiology and immunology that is important for the healing of muscle tissue. We’ve revealed the interactions, and we’re talking about a new form of mechanotherapy that can be as powerful as chemotherapy or genetic therapy, but much simpler and less invasive, “said Wyss. Directors Don Ingber, MD, Ph.D. Says. Judah Folkman Professor of Vascular Biology Professor of Vascular Biology Program at (HMS) and Boston Children’s Hospital, and Bioengineering at SEAS.
Reference: “Regeneration of skeletal muscle with clearance of neutrophils through robotic action” October 6, 2021 Scientific translation medicine..
Additional authors of this treatise include Benjamin Freedman, Brian Kwee, Sungmin Nam, Irenede Lázaro, Max Darnell, Jonathan Alvarez, Maxence Dellacherie, and Herman H. Vandenburgh of Brown University at Wyss Institute and SEAS.
This research was supported by the National Institute of Dental and Cranio-Facial Research Award No. R01DE013349, the Eunice Kennedy Schreiber National Institute of Pediatric Health and Human Development Award No. P2CHD086843, and the Center for Materials Research Science and Technology grant DMR-1420570. National Science Foundation, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institute of Health (F32 AG057135), and National Cancer Institute (U01CA214369).
Massage not only feels good, but also accelerates and strengthens muscle healing
https://scitechdaily.com/muscle-regeneration-massage-doesnt-just-feel-good-it-makes-muscles-heal-faster-and-stronger/ Massage not only feels good, but also accelerates and strengthens muscle healing