A platform to investigate multi-tissue crosstalk mediated by exercise induced soluble factors released from human skeletal muscle

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The benefits of exercise are well documented, whereby people regularly undertaking some form of physical activity score highly in measures of fitness, health and mental wellbeing. Exercise is also known to reduce the likelihood of developing a number of diseases including (but not limited to): type 2 diabetes, dementia and cancer. Participation in exercise does not cause severe side effects, and in many cases is considered as effective as some prescribed medical interventions in the cure and reduction of symptoms. However, despite these clear advantages, exercise is rarely used as a clinical intervention. One reason for its infrequent use is that individuals respond differently to the same exercise intervention, with some people not responding at all. Additionally, a specific exercise intervention may improve one health outcome but not another, an effect that is increasingly variable between patients. This makes exercise prescription challenging. To overcome this, we need new methods of determining whether exercise interventions are effective for the specific organ/tissue (e.g. liver or muscle) being targeted, and whether each unique patient is responsive to that mode of treatment. As skeletal muscle adapts to exercise it also communicates with other organs and tissues both directly (e.g. bone) and indirectly (e.g. pancreas). This phenomenon is termed crosstalk. Our current understanding of this crosstalk is that biological materials (named exerkines) are released as we exercise and are able to travel between tissue/organs. Latest studies suggest that this crosstalk may be responsible for many of the health benefits associated with exercise. These current studies have been conducted in both humans and animals during exercise. However, the biological complexity of animals and humans makes it difficult to model crosstalk associated with a single tissue, as the rest of the bodily functions mask these signals. These studies are also expensive, time consuming, and in the case of animal modelling unethical. Therefore, we need new methods (not using humans/animals) that allow us to understand more about the role of exerkines, and determine their effect on other tissues. To achieve this, this research will: a) recreate protocols that mimic skeletal muscle during exercise within lab grown tissues, b) measure and monitor the exerkines produced during this exercise c) administer these exerkines to other tissues (e.g. bones) so we can understand how they affect different parts of the body. The long-term vision of this work is that we can reduce, and ultimately replace, the animal models currently used in this research, and provide a way of modelling tissue crosstalk that allows us to assess biological crosstalk in a level of detail in which existing models cannot.