Animal models, such as mice, are used in many scientific studies, including in cases where studying living humans would be impractical. For example, many studies have used mice to attempt to predict human muscle properties, as the necessary measurements require highly invasive surgery that includes removal of the muscle from the body. Recently, a research team led by the Shirley Ryan AbilityLab leveraged a rare and unique surgical technique to directly study the muscle of living human patients who required muscle transplant surgery, revealing the limitations of using animal models to accurately estimate human muscle properties.
The study was conducted during surgical procedures in which each patient’s gracilis muscle was removed from their thigh and transplanted into their arm to restore elbow flexion after a brachial plexus injury. During the surgeries, the researchers were able to measure the force-length relationship of the gracilis muscle and calculate its optimal fiber length from the length-tension measurements. The data from the living human patients were compared with computational models derived from small mammal studies, as well as with data obtained from anatomical studies of cadavers.
The researchers found that the human muscle fiber-specific tension is 24% smaller than believed based on scaled-up data from studies of small mammal muscles. The average gracilis optimal fiber length of the living patients was also found to be half of what it was predicted to be based on studies of human cadavers. The team was able to determine that the gracilis is composed of relatively short fibers acting in parallel, rather than long fibers as believed from extrapolating information from animal models. This study was published in The Journal of Physiology.
“When extrapolating from mice to humans, some scaling laws work beautifully, such as when measuring cardiac output and blood pressure. However, through this study we’ve demonstrated that the same scaling principles don’t apply in the muscle, and are in fact highly nonlinear,” said senior author Richard L. Lieber, chief scientific officer at Shirley Ryan AbilityLab, professor at Northwestern University and senior research scientist at the Edward Hines Jr. VA Hospital. “Moving forward, we shouldn’t conduct a mouse muscle study and then simply multiply by body size to predict human properties.”
This research could have significant implications for a number of disciplines, including surgery, muscle rehabilitation therapy, and computational musculoskeletal modeling. Lieber believes these insights represent a path forward to better understand human muscle performance and recognize the limitations of current animal-based models.