Dynamic quantification of host Schwann cell migration into peripheral nerve allografts
Copyright © 2010 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2010 |
|---|---|
| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:225 |
|---|---|
| Enthalten in: |
Experimental neurology - 225(2010), 2 vom: 10. Okt., Seite 310-9 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Whitlock, Elizabeth L [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 01.10.2010 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1016/j.expneurol.2010.07.001 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM199606498 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM199606498 | ||
| 003 | DE-627 | ||
| 005 | 20231223214959.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231223s2010 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.expneurol.2010.07.001 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n0665.xml |
| 035 | |a (DE-627)NLM199606498 | ||
| 035 | |a (NLM)20633557 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Whitlock, Elizabeth L |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dynamic quantification of host Schwann cell migration into peripheral nerve allografts |
| 264 | 1 | |c 2010 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 01.10.2010 | ||
| 500 | |a Date Revised 03.12.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2010 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a CD40 Antigens |2 NLM | |
| 650 | 7 | |a Immunosuppressive Agents |2 NLM | |
| 650 | 7 | |a S100 Proteins |2 NLM | |
| 650 | 7 | |a Caspase 3 |2 NLM | |
| 650 | 7 | |a EC 3.4.22.- |2 NLM | |
| 650 | 7 | |a Tacrolimus |2 NLM | |
| 650 | 7 | |a WM0HAQ4WNM |2 NLM | |
| 700 | 1 | |a Myckatyn, Terence M |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Alice Y |e verfasserin |4 aut | |
| 700 | 1 | |a Yee, Andrew |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Magill, Christina K |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Philip J |e verfasserin |4 aut | |
| 700 | 1 | |a Mackinnon, Susan E |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Experimental neurology |d 1959 |g 225(2010), 2 vom: 10. Okt., Seite 310-9 |w (DE-627)NLM000016624 |x 1090-2430 |7 nnns |
| 773 | 1 | 8 | |g volume:225 |g year:2010 |g number:2 |g day:10 |g month:10 |g pages:310-9 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.expneurol.2010.07.001 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 225 |j 2010 |e 2 |b 10 |c 10 |h 310-9 | ||