M.S. Defense Seminar

David E. Abplanalp

Thursday, July 20, 2017

Med 1-7619 - Adolph Auditorium Medical Center

“The Murphy Roths Large (MRL/MpJ) “Super-Healer” Mouse as a Model of Scarless Flexor Tendon Healing”

Injuries to the flexor tendons of the hands can have significantly harmful outcomes for patients unfortunate enough to sustain such an injury.  In addition to the naturally poor healing ability of tendons, the nearby presence of a synovial sheath and fibro-osseous pulley systems can result in the formation of debilitating adhesions between the tendon and surrounding anatomical constructs.  Adhesion formation results in severely restricted range of motion and in severe cases can require a second surgical intervention.  The inflammatory system has long been known to play a significant role in the healing response heavily favoring an aggressive wound closing deposition of extracellular matrix proteins that are slowly remodeled to form a mature scar.  A unique mouse model, the MRL/MpJ, has been shown to exhibit significantly improved adult healing in a variety of musculoskeletal tissues compared to other common control strains.  Due to the autoimmune prone nature of this mouse, it presents with a different immune system than common controls and would likely display a different inflammatory response to injury as a result.  Employing a clinically relevant model of flexor tendon laceration, it was shown that MRL mice exhibited a blunted systemic immune response to injury compared to C57 controls.  Upon evaluation of histology MRL mice presented with less apparent inflammation, a shortened healing timeline, and decreased formation of adhesions.  Local gene expression analysis showed upregulation of matrix depositing/ remodeling genes resulting in elevated wound matrix turnover.  These results confirm that the MRL mounts an altered inflammatory response to injury and further indicate they play an important role in the improved healing observed.