title: ADSCs in a fibrin matrix enhance nerve regeneration after epineural suturing in a rat model.
abstract: BACKGROUND
  Due to their unique properties, adipose derived stem cells (ADSCs) obtain promising potential to enhance nerve regeneration. The aim of this study was to investigate if fibrin-glue embedded ADSCs were a beneficial adjunct to primary coaptation in a rat sciatic nerve model.
  
  
  METHODS
  Fifty male Lewis rats underwent sciatic nerve transection and subsequent epineural suture repair. The treatment group received ADSCs re-suspended in fibrin glue, while the control group received fibrin glue only. After 7, 21, 35, and 63 days, analysis involved axon count, myelin sheath thickness as well as N- and G-ratios. Additionally, muscle weight quotient (operated vs. non-operated site of the same animal) was calculated and compared between treatment and control groups. For co-detection of vital ADSCs, vessel walls, and Schwann cells, immunolabeling was performed with CM-DiI, SMA, and S-100 antibodies, respectively.
  
  
  RESULTS
  ADSCs led to a significant increase of myelinization at day 21 (0.508 ± 0.085 μm vs. 0.381 ± 0.044 μm, P = 0.025) and day 35 (0.872 ± 0.09 µm vs. 0.495 ± 0.078 µm; P = 0.01) after surgery. Axon count was significantly increased at day 21 (420 ± 119 vs. 129 ± 63; P = 0.003) and day 63 (284 ± 137 vs. 111 ± 26; P = 0.046) after surgery. N- and G-ratios were significantly different compared with control indicating enhanced nerve regeneration due to ADSC treatment at each time point (P < 0.05). Muscle weight quotient was significantly higher in the treatment group compared with the control at day 21 (44.01% ± 6.16% vs. 35.03% ± 2.61%; P = 0.014) and day 63 (65.49% ± 2.81% vs. 58.79% ± 4.06%; P = 0.009) after surgery. Co-detection of immunolabeled cells showed vital ADSCs at the neuronal repair site and in close proximity to intraneuronal vessels indicating active participation of ADSCs in the process of nerve regeneration and associated angiogenesis.
  
  
  CONCLUSIONS
  ADSCs embedded in a fibrin matrix can significantly enhance regeneration of peripheral nerve injuries after primary coaptation. © 2015 Wiley Periodicals, Inc. Microsurgery 36:491-500, 2016.
authors.affiliation: ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Matthias A
authors.initials: MA
authors.lastname: Reichenberger
authors.affiliation: University Hospital Leipzig, Department of Neuropathology, University of Leipzig, Leipzig, Germany.
authors.forename: Wolf
authors.initials: W
authors.lastname: Mueller
authors.affiliation: ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hartmann
authors.affiliation: BG Trauma Centre Ludwigshafen, Clinic for Hand, Plastic and Reconstructive Surgery, Burn Centre, Hand and Plastic Surgery of the University of Heidelberg, Heidelberg, Germany.
authors.forename: Yannick
authors.initials: Y
authors.lastname: Diehm
authors.affiliation: Clinical Cooperation Unit Neuropathology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lass
authors.affiliation: ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Koellensperger
authors.affiliation: ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Leimer
authors.affiliation: ETHIANUM-Clinic for Plastic and Reconstructive Surgery, Aesthetic and Preventive Medicine at Heidelberg University Hospital, Heidelberg, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Germann
authors.affiliation: BG Trauma Centre Ludwigshafen, Clinic for Hand, Plastic and Reconstructive Surgery, Burn Centre, Hand and Plastic Surgery of the University of Heidelberg, Heidelberg, Germany. Sebastian.fischer@bgu-ludwigshafen.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Fischer
mesh_terms: D000818:Animals; D003131:Combined Modality Therapy; D015718:Fibrin Tissue Adhesive; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D009416:Nerve Regeneration / Q000502:physiology*; D059348:Peripheral Nerve Injuries / Q000503:physiopathology / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D012584:Sciatic Nerve / Q000293:injuries* / Q000502:physiology / Q000601:surgery; D050151:Subcutaneous Fat / Q000166:cytology; D013536:Suture Techniques; D014014:Tissue Adhesives; D016896:Treatment Outcome
chemical_list: D015718:Fibrin Tissue Adhesive; D014014:Tissue Adhesives