Research articleRegeneration patterns influence hindlimb automutilation after sciatic nerve repair using stem cells in rats

- Rat sciatic nerve experimental surgery can lead to neuropathic pain and autophagy.
- Cell therapy has been proposed to improve peripheral nerve regeneration.
- Different stem cells can influence regeneration dynamics and, ultimately, neuropathic pain.
- Recurrent automutilation patterns are detected after sciatic nerve repair.
- Quality of regeneration was inversely related to autophagy.

IntroductionHindlimb autophagy is common after rat sciatic total axotomy and is considered as a sign of neuropathic pain. We applied adult stem cells in a fibrin conduit in a total sciatic axotomy model to improve nerve regeneration, investigating whether a correlation could be detected between stem cells effects on regeneration and limb autophagy.Material and MethodsAfter sciatic nerve section, a 1-cm sciatic gap was crossed using fibrin conduits. Experimental groups included empty fibrin conduits, fibrin conduits seeded with primary Schwann cells, and fibrin conduits seeded with Schwann cell-like differentiated mesenchymal or adipose-derived stem cells (dMSCs and dASCs). Controls were represented by autografts and by sham rats (tot n = 34). At 16 weeks post-implantation, regeneration pattern was analysed on histological sections and related to eventual autophagy. Hindlimbs were evaluated and scored according to autophagy Wall's scale and X-Rays radiological evaluation.ResultsAll regenerative cell lines significantly improved myelination at the mid conduit level, compared to the empty tubes. However, dMSC could not significantly improve myelination at the distal stump, showing a more chaotic regeneration compared to both other cells groups and controls. Autophagy was correlated to this regeneration patterns, with higher autophagy scores in the empty and dMSC group.ConclusionHindlimb autophagy can be used as index of neuropathic pain due to nerve lesion or on-going immature regeneration. dMSC group was characterized by a less targeted regeneration comparing to dASC and primary Schwann cells, which confirmed their effectiveness in regeneration and potential in future clinical applications.