A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration

B. Kern, J. D. Budihardjo, S. Mermulla, A. Quan, C. Cadmi, J. Lopez, M. Khusheim, S. Xiang, J. Park, G. J. Furtmüller, K. A. Sarhane, S. Schneeberger, W. P.A. Lee, A. Hoke, S. H. Tuffaha, G. Brandacher

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Improved nerve regeneration and functional outcomes would greatly enhance the utility of vascularized composite allotransplantation (VCA) such as hand and upper extremity transplantation. However, research aimed at achieving this goal has been limited by the lack of a functional VCA animal model. We have developed a novel rat midhumeral forelimb transplant model that allows for the characterization of upper extremity functional recovery following transplantation. At the final end point of 12 weeks, we found that animals with forelimb transplantation including median, ulnar and radial nerve coaptation demonstrated significantly improved grip strength and forelimb function as compared to forelimb transplantation without nerve approximation (grip strength: 1.71N ± 0.57 vs. no appreciable recovery; IBB scale: 2.6 ± 0.7? vs. 0.8 ± 0.40; p = 0.0005), and similar recovery to nerve transection-and-repair only (grip strength: 1.71N ± 0.57 vs. 2.03 ± 0.42.6; IBB scale: 2.6 ± 0.7 vs. 2.8 ± 0.8; p = ns). Moreover, all forelimb transplant animals with nerve coaptation displayed robust axonal regeneration with myelination and reduced flexor muscle atrophy when compared to forelimb transplant animals without nerve coaptation. In conclusion, this is the first VCA small-animal model that allows for reliable and reproducible measurement of behavioral functional recovery in addition to histologic evaluation of nerve regeneration and graft reinnervation.

Original languageEnglish (US)
Pages (from-to)622-634
Number of pages13
JournalAmerican Journal of Transplantation
Volume17
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Keywords

  • animal models: murine
  • basic (laboratory) research/science
  • diagnostic techniques and imaging
  • neurology
  • rehabilitation
  • translational research/science
  • vascularized composite and reconstructive transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)

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  • Cite this

    Kern, B., Budihardjo, J. D., Mermulla, S., Quan, A., Cadmi, C., Lopez, J., Khusheim, M., Xiang, S., Park, J., Furtmüller, G. J., Sarhane, K. A., Schneeberger, S., Lee, W. P. A., Hoke, A., Tuffaha, S. H., & Brandacher, G. (2017). A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration. American Journal of Transplantation, 17(3), 622-634. https://doi.org/10.1111/ajt.14007