Advanced

Peripheral nerve reconstruction. Studies on cellular and acellular iso-, allo- and xenografts

Kvist, Martin LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:12.
Abstract
The best results after a nerve injury with a defect are achieved by a nerve reconstruction procedure

using autologous nerve grafts. However, limitations include insufficient amount of suitable donor

material and donor site morbidity. The aim of the present thesis was to study alternative nerve grafts,

i.e. allo- and xenografts, in rats and mice. Cellular grafts will evoke a rejection in the host aiming at

destroying the graft. Thus, different strategies to suppress or avoid rejection were studied.

Treatment with the immunosuppressant FK506 increased axonal outgrowth after a nerve crush lesion,

but did not improve axonal outgrowth in autologous nerve grafts in rats.

... (More)
The best results after a nerve injury with a defect are achieved by a nerve reconstruction procedure

using autologous nerve grafts. However, limitations include insufficient amount of suitable donor

material and donor site morbidity. The aim of the present thesis was to study alternative nerve grafts,

i.e. allo- and xenografts, in rats and mice. Cellular grafts will evoke a rejection in the host aiming at

destroying the graft. Thus, different strategies to suppress or avoid rejection were studied.

Treatment with the immunosuppressant FK506 increased axonal outgrowth after a nerve crush lesion,

but did not improve axonal outgrowth in autologous nerve grafts in rats.

The new strategy of costimulation blockade that inhibits T-cell activation prohibited rejection of nerve

allografts in mice in the short term. Rejection of grafts in placebo-treated mice impeded axonal out-

growth. In the long-term, costimulation blockade inhibited rejection and resulted in an improved

myelination of regenerated axons. A higher target muscle weight indicated less denervation atrophy

and thus improved nerve regeneration after costimulation blockade.

To avoid immunosuppression altogether acellular nerve allo- and xenografts were studied. The best

axonal outgrowth was observed in allografts. The axonal outgrowth in xenografts was influenced by

the combination of host/donor species.



In conclusion, costimulation blockade inhibits rejection of nerve allografts and allows axonal outgrowth.

However, for reconstruction of an isolated severe nerve injury with a defect, the use of acellular nerve

allografts is a promising strategy. It addresses many of the limitations of autologous nerve grafts without

necessitating immunosuppression. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Terenghi, Giorgio, Manchester, Storbritannien
organization
publishing date
type
Thesis
publication status
published
subject
keywords
acellular nerve graft, costimulation blockade, FK506, immunosuppression, nerve graft, nerve defect, nerve regeneration, nerve injury, nerve extraction, allograft, xenograft
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:12
pages
116 pages
publisher
Lund University, Dept of Hand Surgery
defense location
Lilla aulan, Medicinskt Forskningscentrum, Ingång 59, Skånes Universitetssjukhus, Malmö,
defense date
2010-03-05 13:00
ISSN
1652-8220
ISBN
978-91-86443-26-9
language
English
LU publication?
yes
id
837dc867-a04a-43cf-9a7c-46c91377579e (old id 1544285)
date added to LUP
2010-02-12 12:23:43
date last changed
2018-05-29 12:09:41
@phdthesis{837dc867-a04a-43cf-9a7c-46c91377579e,
  abstract     = {The best results after a nerve injury with a defect are achieved by a nerve reconstruction procedure <br/><br>
 using autologous nerve grafts. However, limitations include insufficient amount of suitable donor <br/><br>
 material and donor site morbidity. The aim of the present thesis was to study alternative nerve grafts, <br/><br>
 i.e. allo- and xenografts, in rats and mice. Cellular grafts will evoke a rejection in the host aiming at <br/><br>
 destroying the graft. Thus, different strategies to suppress or avoid rejection were studied.<br/><br>
 Treatment with the immunosuppressant FK506 increased axonal outgrowth after a nerve crush lesion, <br/><br>
 but did not improve axonal outgrowth in autologous nerve grafts in rats.<br/><br>
 The new strategy of costimulation blockade that inhibits T-cell activation prohibited rejection of nerve <br/><br>
 allografts in mice in the short term. Rejection of grafts in placebo-treated mice impeded axonal out-<br/><br>
 growth. In the long-term, costimulation blockade inhibited rejection and resulted in an improved <br/><br>
 myelination of regenerated axons. A higher target muscle weight indicated less denervation atrophy <br/><br>
 and thus improved nerve regeneration after costimulation blockade.<br/><br>
 To avoid immunosuppression altogether acellular nerve allo- and xenografts were studied. The best <br/><br>
 axonal outgrowth was observed in allografts. The axonal outgrowth in xenografts was influenced by <br/><br>
 the combination of host/donor species.<br/><br>
 <br/><br>
 In conclusion, costimulation blockade inhibits rejection of nerve allografts and allows axonal outgrowth. <br/><br>
 However, for reconstruction of an isolated severe nerve injury with a defect, the use of acellular nerve <br/><br>
 allografts is a promising strategy. It addresses many of the limitations of autologous nerve grafts without <br/><br>
 necessitating immunosuppression.},
  author       = {Kvist, Martin},
  isbn         = {978-91-86443-26-9},
  issn         = {1652-8220},
  keyword      = {acellular nerve graft,costimulation blockade,FK506,immunosuppression,nerve graft,nerve defect,nerve regeneration,nerve injury,nerve extraction,allograft,xenograft},
  language     = {eng},
  pages        = {116},
  publisher    = {Lund University, Dept of Hand Surgery},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Peripheral nerve reconstruction. Studies on cellular and acellular iso-, allo- and xenografts},
  volume       = {2010:12},
  year         = {2010},
}