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IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation

Kostereva, NV and Wang, Y and Fletcher, DR and Unadkat, JV and Schnider, JT and Komatsu, C and Yang, Y and Stolz, DB and Davis, MR and Plock, JA and Gorantla, VS (2016) IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation. PLoS ONE, 11 (6).

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Impaired nerve regeneration and inadequate recovery of motor and sensory function following peripheral nerve repair remain the most significant hurdles to optimal functional and quality of life outcomes in vascularized tissue allotransplantation (VCA). Neurotherapeutics such as Insulin-like Growth Factor-1 (IGF-1) and chondroitinase ABC (CH) have shown promise in augmenting or accelerating nerve regeneration in experimental models and may have potential in VCA. The aim of this study was to evaluate the efficacy of low dose IGF-1, CH or their combination (IGF-1+CH) on nerve regeneration following VCA. We used an allogeneic rat hind limb VCA model maintained on low-dose FK506 (tacrolimus) therapy to prevent rejection. Experimental animals received neurotherapeutics administered intraoperatively as multiple intraneural injections. The IGF-1 and IGF-1+CH groups received daily IGF-1 (intramuscular and intraneural injections). Histomorphometry and immunohistochemistry were used to evaluate outcomes at five weeks. Overall, compared to controls, all experimental groups showed improvements in nerve and muscle (gastrocnemius) histomorphometry. The IGF-1 group demonstrated superior distal regeneration as confirmed by Schwann cell (SC) immunohistochemistry as well as some degree of extrafascicular regeneration. IGF-1 and CH effectively promote nerve regeneration after VCA as confirmed by histomorphometric and immunohistochemical outcomes.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Kostereva, NV
Wang, Y
Fletcher, DR
Unadkat, JV
Schnider, JT
Komatsu, Cchk90@pitt.eduCHK90
Yang, Y
Stolz, DBdonna.stolz@pitt.eduDSTOLZ
Davis, MR
Plock, JA
Gorantla, VSvsg2@pitt.eduVSG2
ContributionContributors NameEmailPitt UsernameORCID
Centers: Other Centers, Institutes, Offices, or Units > Center for Biologic Imaging
Other Centers, Institutes, Offices, or Units > McGowan Institute for Regenerative Medicine
Other Centers, Institutes, Offices, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 June 2016
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS ONE
Volume: 11
Number: 6
DOI or Unique Handle: 10.1371/journal.pone.0156149
Institution: University of Pittsburgh
Refereed: Yes
Date Deposited: 22 Dec 2016 16:03
Last Modified: 02 Apr 2021 19:55


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