Unlabelled: 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.
Teaser: Proteins enriched in a super-healer mouse strain elicit interspecies utility in promoting pro-regenerative tenocyte behavior.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11257490 | PMC |
| http://dx.doi.org/10.1101/2024.07.08.602500 | DOI Listing |
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Unlabelled: 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.
View Article and Find Full Text PDFRegenerative MRL/MpJ tendon cells exhibit sex differences in morphology, proliferation, mechanosensitivity, and cell-ECM organization.
J Orthop Res
October 2023
Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York, USA.
Clinical and animal studies have reported the influence of sex on the incidence and progression of tendinopathy, which results in disparate structural and biomechanical outcomes. However, there remains a paucity in our understanding of the sex-specific biological mechanisms underlying effective tendon healing. To overcome this hurdle, our group has investigated the impact of sex on tendon regeneration using the super-healer Murphy Roths Large (MRL/MpJ) mouse strain.
View Article and Find Full Text PDFEarlier proteoglycan turnover promotes higher efficiency matrix remodeling in MRL/MpJ tendons.
J Orthop Res
October 2023
Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA.
While most mammalian tissue regeneration is limited, the Murphy Roths Large (MRL/MpJ) mouse has been identified to regenerate several tissues, including tendon. Recent studies have indicated that this regenerative response is innate to the tendon tissue and not reliant on a systemic inflammatory response. Therefore, we hypothesized that MRL/MpJ mice may also exhibit a more robust homeostatic regulation of tendon structure in response to mechanical loading.
View Article and Find Full Text PDFEnhanced healing outcomes in MRL/MpJ mouse tissues conserved in insertion site following surgical repair.
J Shoulder Elbow Surg
December 2022
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA; Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA; Hospital for Special Surgery, New York, NY, USA. Electronic address:
Background: Surgical repair of supraspinatus tendons (SSTs) has a high failure rate at the insertion site. A significant hurdle to therapeutic development is that effective intrinsic healing mechanisms are unknown. The MRL/MpJ (MRL) mouse exhibits tissue-specific enhanced healing; however, these tissues exhibit disparate properties from the complex SST.
View Article and Find Full Text PDFAltered TGFB1 regulated pathways promote accelerated tendon healing in the superhealer MRL/MpJ mouse.
Sci Rep
February 2022
Department of Biomedical Engineering, University of Rochester, Rochester, NY, USA.
Article Synopsis
- Researchers studied MRL mice, a model for tissue regeneration, to investigate how tendons heal compared to C57 mice, finding that MRL tendons showed faster recovery and less scarring.
- RNA sequencing revealed that different healing mechanisms were at play, with C57 mice exhibiting pathways linked to inflammation and fibrosis, while MRL mice showed a focus on cell cycle regulation.
- Analysis of proteins in blood samples indicated that MRL mice had lower levels of certain inflammatory markers, suggesting that their unique healing processes could offer insights for enhancing tendon repair in humans.
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