In Vitro, In Vivo and Ex Vivo Models for Peripheral Nerve Injury and
Regeneration

Li, Andrew; Pereira, Clifford T.; Hill, Elise Eleanor; Vukcevich, Olivia; Wang, Aijun

doi:10.2174/1570159x19666210407155543

Cited by 13 publications

(8 citation statements)

References 157 publications

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“…Due to the fact primary cells have limited proliferation potential and develop senescence ( Monje, 2020 ), there is a challenge in obtaining sufficient cell numbers in vitro . To circumvent this limitation, SCs can be immortalized or isolated from neoplastic tissues ( Li et al, 2022 ).…”

Section: Preclinical Studies and In Vitro Protocol...mentioning

confidence: 99%

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Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment

Oliveira,

Yanick,

Wein

et al. 2023

Front. Cell. Neurosci.

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Schwann cells (SCs) have a critical role in the peripheral nervous system. These cells are able to support axons during homeostasis and after injury. However, mutations in genes associated with the SCs repair program or myelination result in dysfunctional SCs. Several neuropathies such as Charcot–Marie–Tooth (CMT) disease, diabetic neuropathy and Guillain–Barré syndrome show abnormal SC functions and an impaired regeneration process. Thus, understanding SCs-axon interaction and the nerve environment in the context of homeostasis as well as post-injury and disease onset is necessary. Several neurotrophic factors, cytokines, and regulators of signaling pathways associated with proliferation, survival and regeneration are involved in this process. Preclinical studies have focused on the discovery of therapeutic targets for peripheral neuropathies and injuries. To study the effect of new therapeutic targets, modeling neuropathies and peripheral nerve injuries (PNIs) in vitro and in vivo are useful tools. Furthermore, several in vitro protocols have been designed using SCs and neuron cell lines to evaluate these targets in the regeneration process. SCs lines have been used to generate effective myelinating SCs without success. Alternative options have been investigated using direct conversion from somatic cells to SCs or SCs derived from pluripotent stem cells to generate functional SCs. This review will go over the advantages of these systems and the problems associated with them. In addition, there have been challenges in establishing adequate and reproducible protocols in vitro to recapitulate repair SC-neuron interactions observed in vivo. So, we also discuss the mechanisms of repair SCs-axon interactions in the context of peripheral neuropathies and nerve injury (PNI) in vitro and in vivo. Finally, we summarize current preclinical studies evaluating transgenes, drug, and novel compounds with translational potential into clinical studies.

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Section: Preclinical Studies and In Vitro Protocol...mentioning

confidence: 99%

“…50B11 is a sensory neuron cell line isolated from rat embryonic DRG ( Chen et al, 2007 ). This cell line is also used for neurite outgrowth assays ( Li et al, 2022 ).…”

Section: Preclinical Studies and In Vitro Protocol...mentioning

confidence: 99%

Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment

Oliveira,

Yanick,

Wein

et al. 2023

Front. Cell. Neurosci.

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“…It is prudent to observe overall physiological reactions and compare them to the current gold standard (positive control variable) and clinical care needed to determine the efficacy of the implant towards its intended targeted therapy. This essential step requires careful selection of the model system, variable control, and access, depending on the application of the implant and the current standardized ISO and ASTM guidelines for in vivo testing [ 34 , 35 ].…”

Section: Biocompatibility Assessmentmentioning

confidence: 99%

“…The controlled variables should also be focused towards answering specific questions related to the assessment of biomaterials in one or all domains of in vivo biomaterial assessments (biocompatibility testing, bioactivity testing, or preclinical testing). Meanwhile, these variables should retain the ability to translate these control parameters to alternative or more complex animal models [ 34 , 35 ].…”

Section: Biocompatibility Assessmentmentioning

confidence: 99%

“…Additionally, the studies using rat models most commonly used quantitative histology analysis to assess nerve healing, followed by nerve morphometric analysis, electrophysiology, and immunohistology, respectively. The number of animal parameters to consider and the degree of control between model variables has created problems among investigators in establishing a consensus on the best animal model design and methods for assessing nerve recovery [ 34 , 35 , 36 ].…”

Section: Biocompatibility Assessmentmentioning

confidence: 99%

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Interactions of Cells and Biomaterials for Nerve Tissue Engineering: Polymers and Fabrication

Harley-Troxell,

Steiner,

Advincula

et al. 2023

Polymers

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Neural injuries affect millions globally, significantly impacting their quality of life. The inability of these injuries to heal, limited ability to regenerate, and the lack of available treatments make regenerative medicine and tissue engineering a promising field of research for developing methods for nerve repair. This review evaluates the use of natural and synthetic polymers, and the fabrication methods applied that influence a cell’s behavior. Methods include cross-linking hydrogels, incorporation of nanoparticles, and 3D printing with and without live cells. The endogenous cells within the injured area and any exogenous cells seeded on the polymer construct play a vital role in regulating healthy neural activity. This review evaluates the body’s local and systemic reactions to the implanted materials. Although numerous variables are involved, many of these materials and methods have exhibited the potential to provide a biomaterial environment that promotes biocompatibility and the regeneration of a physical and functional nerve. Future studies may evaluate advanced methods for modifying material properties and characterizing the tissue–biomaterial interface for clinical applications.

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In Vitro Models for Peripheral Nerve Regeneration

Tusnim,

Kutuzov,

Grasman

2024

Adv Healthcare Materials

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Peripheral nerve injury (PNI) resulting in lesions is highly prevalent clinically, but current therapeutic approaches fail to provide satisfactory outcomes in many patients. While peripheral nerves have intrinsic regenerative capacity, the regenerative capabilities of peripheral nerves are often insufficient to restore full functionality. This highlights an unmet need for developing more effective strategies to repair damaged peripheral nerves and improve regenerative success. Consequently, researchers are actively exploring a variety of therapeutic strategies, encompassing the local delivery of trophic factors or bioactive molecules, the design of advanced biomaterials that interact with regenerating axons, and augmentation with nerve guidance conduits or complex prostheses. However, clinical translation of these technologies remains limited, emphasizing the need for continued research on peripheral nerve regeneration modalities that can enhance functional restoration. Experimental models that accurately recapitulate key aspects of peripheral nerve injury and repair biology can accelerate therapeutic development by enabling systematic testing of new techniques. Advancing regenerative therapies for PNI requires bridging the gap between basic science discoveries and clinical application. This review discusses different in vitro models of peripheral nerve injury and repair, including their advantages, limitations, and potential applications.

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In Vitro, In Vivo and Ex Vivo Models for Peripheral Nerve Injury and Regeneration

Cited by 13 publications

References 157 publications

Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment

Neuron-Schwann cell interactions in peripheral nervous system homeostasis, disease, and preclinical treatment

Interactions of Cells and Biomaterials for Nerve Tissue Engineering: Polymers and Fabrication

In Vitro Models for Peripheral Nerve Regeneration

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