| Dynamic quantification of host Schwann cell migration into peripheral nerve allografts. | |
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MedLine Citation:
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PMID: 20633557 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Elizabeth L Whitlock; Terence M Myckatyn; Alice Y Tong; Andrew Yee; Ying Yan; Christina K Magill; Philip J Johnson; Susan E Mackinnon |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2010-07-12 |
Journal Detail:
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Title: Experimental neurology Volume: 225 ISSN: 1090-2430 ISO Abbreviation: Exp. Neurol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-13 Completed Date: 2010-10-01 Revised Date: 2012-05-07 |
Medline Journal Info:
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Nlm Unique ID: 0370712 Medline TA: Exp Neurol Country: United States |
Other Details:
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Languages: eng Pagination: 310-9 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Division of Plastic and Reconstructive Surgery, Washington University School of Medicine, Saint Louis, MO, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Analysis of Variance Animals Antibodies, Monoclonal / pharmacology Antigens, CD40 / immunology Blotting, Western Caspase 3 / immunology, metabolism Cell Movement / immunology, physiology* Immunohistochemistry Immunosuppression / methods Immunosuppressive Agents / pharmacology Mice Mice, Transgenic Nerve Regeneration / immunology, physiology* S100 Proteins / immunology, metabolism Schwann Cells / immunology, physiology* Sciatic Nerve / immunology, physiology, transplantation* Tacrolimus / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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5R01NS033406/NS/NINDS NIH HHS; R01 NS033406-15/NS/NINDS NIH HHS; R01 NS033406-17/NS/NINDS NIH HHS; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Antigens, CD40; 0/Immunosuppressive Agents; 0/S100 Proteins; 109581-93-3/Tacrolimus; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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