title: Dynamic quantification of host Schwann cell migration into peripheral nerve allografts.
abstract: Host Schwann cell (SC) migration into nerve allografts is the limiting factor in the duration of immunosuppression following peripheral nerve allotransplantation, and may be affected by different immunosuppressive regimens. Our objective was to compare SC migration patterns between clinical and experimental immunosuppression regimens both over time and at the harvest endpoint. Eighty mice that express GFP under the control of the Schwann cell specific S100 promoter were engrafted with allogeneic, nonfluorescent sciatic nerve grafts. Mice received immunosuppression with either tacrolimus (FK506), or experimental T-cell triple costimulation blockade (CSB), consisting of CTLA4-immunoglobulin fusion protein, anti-CD40 monoclonal antibody, and anti-inducible costimulator monoclonal antibody. Migration of GFP-expressing host SCs into wild-type allografts was assessed in vivo every 3 weeks until 15 weeks postoperatively, and explanted allografts were evaluated for immunohistochemical staining patterns to differentiate graft from host SCs. Immunosuppression with tacrolimus exhibited a plateau of SC migration, characterized by significant early migration (< 3 weeks) followed by a constant level of host SCs in the graft (15 weeks). At the endpoint, graft fluorescence was decreased relative to surrounding host nerve, and donor SCs persisted within the graft. CSB-treated mice displayed gradually increasing migration of host SCs into the graft, without the plateau noted in tacrolimus-treated mice, and also maintained a population of donor SCs at the 15-week endpoint. SC migration patterns are affected by immunosuppressant choice, particularly in the immediate postoperative period, and the use of a single treatment of CSB may allow for gradual population of nerve allografts with host SCs.
authors.affiliation: Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO, USA.
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: Whitlock
authors.forename: Terence M
authors.initials: TM
authors.lastname: Myckatyn
authors.forename: Alice Y
authors.initials: AY
authors.lastname: Tong
authors.forename: Andrew
authors.initials: A
authors.lastname: Yee
authors.forename: Ying
authors.initials: Y
authors.lastname: Yan
authors.forename: Christina K
authors.initials: CK
authors.lastname: Magill
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Johnson
authors.forename: Susan E
authors.initials: SE
authors.lastname: Mackinnon
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015153:Blotting, Western; D019013:CD40 Antigens / Q000276:immunology; D053148:Caspase 3 / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology / Q000502:physiology*; D007150:Immunohistochemistry; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000276:immunology / Q000502:physiology*; D009418:S100 Proteins / Q000276:immunology / Q000378:metabolism; D012583:Schwann Cells / Q000276:immunology / Q000502:physiology*; D012584:Sciatic Nerve / Q000276:immunology / Q000502:physiology / Q000637:transplantation*; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D007166:Immunosuppressive Agents; D009418:S100 Proteins; D053148:Caspase 3; D016559:Tacrolimus