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 Andrew Lee, Ahmet Hoke, Sami Tuffaha, Gerald Brandacher

Research output: Contribution to journalArticle

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)
JournalAmerican Journal of Transplantation
DOIs
StateAccepted/In press - 2016

Fingerprint

Nerve Regeneration
Forelimb
Rodentia
Vascularized Composite Allotransplantation
Transplantation
Hand Strength
Transplants
Upper Extremity
Animal Models
Radial Nerve
Ulnar Nerve
Muscular Atrophy
Median Nerve
Regeneration
Hand
Research

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
  • Medicine(all)
  • Pharmacology (medical)
  • Transplantation

Cite this

A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration. / 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 Andrew; Hoke, Ahmet; Tuffaha, Sami; Brandacher, Gerald.

In: American Journal of Transplantation, 2016.

Research output: Contribution to journalArticle

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 Andrew ; Hoke, Ahmet ; Tuffaha, Sami ; Brandacher, Gerald. / A Novel Rodent Orthotopic Forelimb Transplantation Model That Allows for Reliable Assessment of Functional Recovery Resulting From Nerve Regeneration. In: American Journal of Transplantation. 2016.
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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.",
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AU - Kern, B.

AU - Budihardjo, J. D.

AU - Mermulla, S.

AU - Quan, A.

AU - Cadmi, C.

AU - Lopez, J.

AU - Khusheim, M.

AU - Xiang, S.

AU - Park, J.

AU - Furtmüller, G. J.

AU - Sarhane, K. A.

AU - Schneeberger, S.

AU - Lee, W P Andrew

AU - Hoke, Ahmet

AU - Tuffaha, Sami

AU - Brandacher, Gerald

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

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KW - Neurology

KW - Rehabilitation

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