Proteins Derived From MRL/MpJ Tendon Provisional Extracellular Matrix and Secretome Promote Pro-Regenerative Tenocyte Behavior

Abstract

Tendinopathies are prevalent musculoskeletal conditions that have no effective therapies to attenuate scar formation. In contrast to other adult mammals, the tendons of Murphy Roths Large (MRL/MpJ) mice possess a superior healing capacity following acute and overuse injuries. Here, we hypothesized that the application of biological cues derived from the local MRL/MpJ tendon environment would direct otherwise scar-mediated tenocytes towards a pro-regenerative MRL/MpJ-like phenotype. We identified soluble factors enriched in the secretome of MRL/MpJ tenocytes using bioreactor systems and quantitative proteomics. We then demonstrated that the combined administration of structural and soluble constituents isolated from decellularized MRL/MpJ tendon provisional ECM (dPECM) and the secretome stimulate scar-mediated rodent tenocytes towards enhanced mechanosensitivity, proliferation, intercellular communication, and ECM deposition associated with MRL/MpJ cell behavior. Our findings highlight key biological mechanisms that drive MRL/MpJ tenocyte activity and their interspecies utility to be harnessed for therapeutic strategies that promote pro-regenerative healing outcomes. TeaserProteins enriched in a super-healer mouse strain elicit interspecies utility in promoting pro-regenerative tenocyte behavior.