The use of sheep as a model for studying peripheral nerve regeneration following nerve injury: review of the literature

Diogo, Camila Cardoso; Camassa, José Arthur de Abreu; Pereira, José Eduardo; Maltez, Luís; Filipe, Vítor; Couto, Pedro; Geuna, Stefano; Maurício, Ana Colette; Varejão, Artur S.P.

doi:10.1080/01616412.2017.1331873

Cited by 39 publications

(37 citation statements)

References 78 publications

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“…Larger animals such as monkeys and sheep are limitedly used in evaluation of peripheral nerve regeneration (Diogo et al, ). One of the benefits of these two models is the possibility of examining large neural gaps using nerve engineering scaffolds.…”

Section: Animal Model For Nerve Regeneration Studymentioning

confidence: 99%

“…One of the benefits of these two models is the possibility of examining large neural gaps using nerve engineering scaffolds. A sheep animal model, due to the great similarity between limb nerves of sheep and humans (Jeans, Gilchrist, & Healy, ), age equality (Fullarton, Lenihan, Myles, & Glasby, ), weight similarity, the ease of keeping, and the lack of moral concern in the society, has recently attracted more attention in the nerve regeneration studies (Diogo et al, ).…”

Section: Animal Model For Nerve Regeneration Studymentioning

confidence: 99%

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The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

Jahromi

Razavi

Bakhtiari

2019

J Tissue Eng Regen Med

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Peripheral nerve damage is a common clinical complication of traumatic injury occurring after accident, tumorous outgrowth, or surgical side effects. Although the new methods and biomaterials have been improved recently, regeneration of peripheral nerve gaps is still a challenge. These injuries affect the quality of life of the patients negatively. In the recent years, many efforts have been made to develop innovative nerve tissue engineering approaches aiming to improve peripheral nerve treatment following nerve injuries. Herein, we will not only outline what we know about the peripheral nerve regeneration but also offer our insight regarding the types of nerve conduits, their fabrication process, and factors associated with conduits as well as types of animal and nerve models for evaluating conduit function. Finally, nerve regeneration in a rat sciatic nerve injury model by nerve conduits has been considered, and the main aspects that may affect the preclinical outcome have been discussed.

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Section: Animal Model For Nerve Regeneration Studymentioning

confidence: 99%

Section: Animal Model For Nerve Regeneration Studymentioning

confidence: 99%

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

Jahromi

Razavi

Bakhtiari

2019

J Tissue Eng Regen Med

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“…To further evaluate the efficacy of ESC in the repair of long (>5 cm) nerve gaps, we tested ESC in a large animal model which provides more accurate and applicable data to advance the ESC to the clinical application. Sheep model was selected due to the morphological resemblance (polyfascicular nerves) of sheep and human peripheral nerves, similar regeneration patterns and the ability to create long nerve defects, which allow for testing of long nerve gaps repair (Diogo et al, ; Forden et al, ; Strasberg et al, ; Ozturk et al, ).…”

Section: Discussionmentioning

confidence: 99%

Application of epineural sheath conduit for restoration of 6‐cm long nerve defects in a sheep median nerve model

et al. 2018

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Background Due to limited number of studies, we tested feasibility of autologous epineural sheath conduit (ESC) in repair of 6‐cm median nerve gaps in a sheep—the large animal model. Materials and methods Eight ewes, 6–8 months old, 30–35 kg, were divided into three experimental groups: group 1—no defect repair (n = 4 nerves/group), group 2—autograft controls (n = 6 nerves/group), group 3—autologous ESC filled with saline (n = 6 nerves/group). ESC was constructed from a 6‐cm long segment of sheep median nerve and tested for expression of laminin B, Glial fibrillary acidic protein (GFAP), S‐100 and CD31 using immunofluorescent staining. At 6 months after nerve repair, nerve conduction velocity and somatosensory evoked potentials (SSEP) assessed neurosensory recovery, while histomorphometry tested nerve regeneration. Results Ex vivo characterization of ESC, before in vivo nerve gap repair, showed high laminin B expression, which supports axonal growth. At 6 months post‐repair, structural integrity of ESC was preserved. ESC was well‐vascularized and tissue adhesions were comparable to autograft controls. The maximal conduction velocities (29.80 ± 5.85 ms vs. 32.28 ± 6.75 ms; p = .44), action potential amplitudes (32.68 ± 17.44 mV vs. 44.14 ± 23.10 mV; p = .38) and SSEP amplitude values (6.18 ± 5.84 mV vs. 4.68 ± 2.53 mV; p = .28) were comparable between autograft and ESC groups. Presence of regenerating axons was confirmed in the distal segment of ESC at 6 months after repair. Conclusion The feasibility of ESC in restoration of 6‐cm long nerve defects in a sheep median nerve model was confirmed by nerve conduction assessments and correlated with axonal regeneration tested by histomorphometry. We confirmed ESC potential in support of regeneration of long nerve defects.

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“…Domestic sheep (Ovis aries) provide unique opportunities in research as an experimental and pre-clinical animal model (Hems and Glasby, 1992;Glasby et al, 1993;Al Abri et al, 2014) because of their availability, low costs and acceptance by the society as a research animal (Diogo et al, 2017). Sheep are docile, easy to handle and relatively inexpensive with respect to housing and feeding.…”

Section: General Considerationsmentioning

confidence: 99%

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

Ribitsch

Baptista

Consiglio

et al. 2020

Front. Bioeng. Biotechnol.

146

110

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Rapid developments in Regenerative Medicine and Tissue Engineering has witnessed an increasing drive toward clinical translation of breakthrough technologies. However, the progression of promising preclinical data to achieve successful clinical market authorisation remains a bottleneck. One hurdle for progress to the clinic is the transition from small animal research to advanced preclinical studies in large animals to test safety and efficacy of products. Notwithstanding this, to draw meaningful and reliable conclusions from animal experiments it is critical that the species and disease model of choice is relevant to answer the research question as well as the clinical problem. Selecting the most appropriate animal model requires in-depth knowledge of specific species and breeds to ascertain the adequacy of the model and outcome measures that closely mirror the clinical situation. Traditional reductionist approaches in animal experiments, which often do not sufficiently reflect the studied disease, are still the norm and can result in a disconnect in outcomes observed between animal studies and clinical trials. To address these concerns a reconsideration in approach will be required. This should include a stepwise approach using in vitro and ex vivo experiments as well as in silico modeling to minimize the need for in vivo studies for screening and early development studies, followed by large animal models which more closely resemble human disease. Naturally occurring, or spontaneous diseases in large animals remain a largely untapped resource, and given the similarities in pathophysiology to humans they not only allow for studying new treatment strategies but also disease etiology and prevention. Naturally occurring disease models, particularly for longer lived large animal species, allow for studying disorders at an age when the disease is most prevalent. As these diseases are usually also a concern in the chosen veterinary species they would be beneficiaries of newly developed therapies. Improved awareness of the progress

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The use of sheep as a model for studying peripheral nerve regeneration following nerve injury: review of the literature

Cited by 39 publications

References 78 publications

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

The advances in nerve tissue engineering: From fabrication of nerve conduit toin vivonerve regeneration assays

Application of epineural sheath conduit for restoration of 6‐cm long nerve defects in a sheep median nerve model

Large Animal Models in Regenerative Medicine and Tissue Engineering: To Do or Not to Do

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