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

Nataliya V. Kostereva, Yong Wang, Derek R. Fletcher, Jignesh V. Unadkat, Jonas T. Schnider, Chiaki Komatsu, Yang Yang, Donna B. Stolz, Michael R. Davis, Jan A. Plock, Vijay S. Gorantla

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0156149
JournalPloS one
Volume11
Issue number6
DOIs
StatePublished - Jun 1 2016

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Vascularized Composite Allotransplantation
Chondroitin ABC Lyase
Nerve Regeneration
somatomedins
Somatomedins
limbs (animal)
nerve tissue
Extremities
Composite materials
Tissue
Tacrolimus
immunohistochemistry
Regeneration
Immunohistochemistry
tacrolimus
injection
Schwann cells
peripheral nerves
Schwann Cells
Intramuscular Injections

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Kostereva, N. V., Wang, Y., Fletcher, D. R., Unadkat, J. V., Schnider, J. T., Komatsu, C., ... Gorantla, V. S. (2016). IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation. PloS one, 11(6), [e0156149]. https://doi.org/10.1371/journal.pone.0156149

IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation. / Kostereva, Nataliya V.; Wang, Yong; Fletcher, Derek R.; Unadkat, Jignesh V.; Schnider, Jonas T.; Komatsu, Chiaki; Yang, Yang; Stolz, Donna B.; Davis, Michael R.; Plock, Jan A.; Gorantla, Vijay S.

In: PloS one, Vol. 11, No. 6, e0156149, 01.06.2016.

Research output: Contribution to journalArticle

Kostereva, NV, Wang, Y, Fletcher, DR, Unadkat, JV, Schnider, JT, Komatsu, C, Yang, Y, Stolz, DB, Davis, MR, Plock, JA & Gorantla, VS 2016, 'IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation', PloS one, vol. 11, no. 6, e0156149. https://doi.org/10.1371/journal.pone.0156149
Kostereva NV, Wang Y, Fletcher DR, Unadkat JV, Schnider JT, Komatsu C et al. IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation. PloS one. 2016 Jun 1;11(6). e0156149. https://doi.org/10.1371/journal.pone.0156149
Kostereva, Nataliya V. ; Wang, Yong ; Fletcher, Derek R. ; Unadkat, Jignesh V. ; Schnider, Jonas T. ; Komatsu, Chiaki ; Yang, Yang ; Stolz, Donna B. ; Davis, Michael R. ; Plock, Jan A. ; Gorantla, Vijay S. / IGF-1 and chondroitinase ABC augment nerve regeneration after vascularized composite limb allotransplantation. In: PloS one. 2016 ; Vol. 11, No. 6.
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