The recovery effect of combined use of tacrolimus and autologous adipocyte derived stem cells on peripheral nerve laceration model on rats

Neuroregenerative process has a great role in maximizing functional recovery after repairing peripheral nerve lacerations. Functional loss occurs at the end-organs due to conduction loss. It is well known that repairing the injured nerve can not recover the function after motor-end plates are degenerated. As a result skeletal muscles should be reinnervated as soon as possible to minimize the functional loss. Various pharmacological agents, surgical methods, stem cell researchs are tested in altering and accelerating nerve regeneration while increasing regeneration quality. Tacrolimus, an immunosuppressive agent which is investigated in neuroregeneration, is found to impore neuroregeneration. In order to avoid side effects of this immunosuppresive agent some researchers administered this drug temporarily and found that it can still play an effective role in neuroregeneration. The neuroregenerative effect of adipocyte derived stem cells are investigated. Several differantiaton status of adypocyte derived stem cells and schwann-like transdifferantiated adipocyte derived stem cells are found to improve nerve regeneration process in peripheral nerve injury models Unfortunately there are some problems about delivering stem cells to the injury site in primary repair models. We have planned to deliver these cells to the repair site by injecting these cells to the perifascicular areolar soft tissue proximally and distally. In this study, we investigated neuroregenerative effects of using tacrolimus and adipocyte derived stem cells together in peripheral nerve laceration model. We have evaluated the funcional recovery by intemittent walking track analysis. Electrophysciological evaluation was made to get compuond muscle action potential and latency duration. Histopathological evaluation was made to understand the quality of regenerating nerves. Wet gastrocnemius muscle weight was assessed and recorded. Walking track analysis showed that subjects that received only stem cells regained walking function better than other subjects (p<0,05). Electrophysological assessments showed that the subjects which receives tacrolimus and stem cells together have shorter latency duration compared to the other nerve injury subjects. In addition Two groups which received stem cells have demonstrated better compuond muscle action potential levels and during the experiment (p<0,05). Groups which treated with stem cells had partially higher wet muscle weight compared to non-stem cell received groups (p>0,05). Histopathological distal to proximal fiber ratio assessment did not demonstrated significant difference between groups (p=0,116). However morphological evaluation showed that non-stem cell received groups had intrafascilular edema and low nerve density. In contrast groups treated with stem cells showed less edema and high density compared to other nerve lacerated groups. In stem cell received groups perifasciular loose tissue contained cells which had S100 dye. Stem cells can enhance compound muscle action potentials and improve functional recovery in laceration models. There are some partial differences between subjects which received only stem cells and tacrolimus with stem cells. However further studies are required to investigate neuroregenerative mechanisms of tacrolimus and adipocyte derived stem cells. Key words: Peripheral nerve regeneration, Tacrolimus, Stem Cells, Walking Track Analysis, Electromyography