The superior healing capacity of MRL tendons is minimally influenced by the systemic environment of the MRL mouse

AbstractMurphy Roths Large mice (MRL) exhibit improved tendon healing and are often described as a “super-healer” strain. The underlying mechanisms that drive the superior healing response of MRL remain a controversial subject. We utilized a tendon transplantation model between MRL and “normal-healer” B6-mice to differentiate between the contribution of MRL’s innate tendon and systemic environment to its improved healing capacity. Patellar tendons with a midsubstance punch injury were transplanted back into the same animal (autograft) or into an animal of the other strain (allograft). Findings at 4 weeks showed that the innate MRL tendon environment drives its improved healing capacity as demonstrated by improved stiffness and maximum load in MRL-grafts-in-B6-host-allografts compared to B6-autografts, and higher modulus in MRL-autografts compared to B6-graft-in-MRL-host-allografts. Groups with an MRL component showed an increase in pro-inflammatory cytokines in the 3 days after injury, suggesting an early enhanced inflammatory profile in MRL that ultimately resolves. A preserved range of motion of the knee joint in all MRL animals suggests a systemic “shielding effect” of MRL in regard to joint adhesiveness. Our findings 4-weeks post injury are consistent with previous studies showing tissue-driven improved healing and suggest that the systemic environment contributes to the overall healing process.