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IN VIVO TECHNOLOGY DEVELOPMENT


PI: Thomas Rando, Professor, Department of Neurology and Neurological Sciences, Stanford University School of Medicine; Chief of the Neurology Service, VA Palo Alto Health Care System; Director, The Glenn Laboratories for the Biology of Aging, Stanford University School of Medicine; Deputy Director, Stanford Center on Longevity, Stanford University

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AR3T is supporting the validation of a system of in vivo noninvasive imaging for assessing muscle stem cell responses to mechanical loading.


The lack of reliable and valid in vivo methods for monitoring exercise-induced alterations in muscle stem cell behavior and myofiber responses over time has been a major obstacle in translating pre-clinical findings into evidence-based practice. While we know that stem cells are exquisitely sensitive to dynamic forces emanating from the microenvironment, there is a gap in our understanding of how stem cells respond to mechanical stimuli experienced in vivo. Traditional pre-clinical models have relied primarily on histological analysis to assess stem cell proliferation, migration and terminal differentiation in animals. However, in addition to being highly labor-intensive, histological analyses are generally terminal for the animal, and therefore require large sample sizes in order to thoroughly understand the temporal regulation of stem cells in response to loading and to tease out dose- and intensity-parameters that affect mechanotransductive cascades. The number of animals necessary to comprehensively address these and other issues has thus far been time- and cost-prohibitive.

Recently developed, a noninvasive bioluminescence imaging system allows for the quantification of muscle stem cell activity as a surrogate measure of disease progression in a murine model. This technology will now be expanded in order to evaluate the effect of muscle contractile activity on muscle stem cell behavior in vivo. It is anticipated that the development of pre-clinical methods that can serve as a rapid read-out of tissue responses to loading will allow for longitudinal testing of multiple rehabilitation protocols at a fraction of the labor and cost.

The goal is to validate a system for the in vivo assessment of muscle stem cell responses to training, which will ultimately advance the science underlying the prescription of exercise protocols for a wide range of disabilities.

Visit the Rando Laboratory website to learn more about regenerative rehabilitation work being done at the Stanford School of Medicine.