AR3T supports the development of in vivo technologies for assessing stem cell responses to mechanical loading.
The lack of reliable and valid in vivo methods for monitoring rehabilitation-induced alterations in 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.
For these reasons, AR3T provides technology development grants to support the development of in vivo technologies, such as noninvasive imaging, that will ultimately advance the science underlying the prescription of exercise protocols for a wide range of disabilities.
Example of an AR3T-funded project: a recently developed, 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 was expanded to evaluate the effect of muscle contractile activity on muscle stem cell behavior in vivo. 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. Visit the Rando Laboratory website to learn more about regenerative rehabilitation work being done at the Stanford School of Medicine.