title: Regeneration patterns influence hindlimb automutilation after sciatic nerve repair using stem cells in rats.
abstract: BACKGROUND
  Hindlimb 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.
  
  
  METHODS
  After 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.
  
  
  RESULTS
  All 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.
  
  
  CONCLUSIONS
  Hindlimb 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.
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Daniel.Haselbach@chuv.ch.
authors.forename: Daniel
authors.initials: D
authors.lastname: Haselbach
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Wassim.Raffoul@chuv.ch.
authors.forename: Wassim
authors.initials: W
authors.lastname: Raffoul
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, Brixen Hospital, South Tyrolean Health Care Service (SABES), Dantersrasse 51-I-3942, Brixen, Italy. Electronic address: lorenz.larcher@gmail.com.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Larcher
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. Electronic address: Mathias.Tremp@usb.ch.
authors.forename: Mathias
authors.initials: M
authors.lastname: Tremp
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Basel, Spitalstrasse 21, CH-4031 Basel, Switzerland. Electronic address: Daniel.Kalbermatten@usb.ch.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Kalbermatten
authors.affiliation: Department of Plastic, Reconstructive and Hand Surgery, University Hospital of Lausanne (CHUV), Rue du Bugnon 46, 1011 Lausanne, Switzerland. Electronic address: Pietro.di-Summa@chuv.ch.
authors.forename: Pietro G
authors.initials: PG
authors.lastname: di Summa
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D053687:Adult Stem Cells / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D001343:Autophagy; D005337:Fibrin; D006614:Hindlimb; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D009416:Nerve Regeneration; D009437:Neuralgia / Q000473:pathology / Q000503:physiopathology; D017207:Rats, Sprague-Dawley; D012583:Schwann Cells / Q000166:cytology / Q000637:transplantation*; D012584:Sciatic Nerve / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D012652:Self Mutilation / Q000473:pathology / Q000503:physiopathology*; D054457:Tissue Scaffolds
chemical_list: D005337:Fibrin
keywords: Autophagy; Neuropathic pain; Regenerative stem cells; Sciatic