Interaction between Schwann cells and other cells during repair of peripheral nerve injury

Neural Regen Res, 2021 · DOI: 10.4103/1673-5374.286956 · Published: January 1, 2021

Regenerative Medicine Neurology Genetics

Simple Explanation

Peripheral nerve injury (PNI) is common, and unlike damage to the central nervous system, injured nerves can effectively regenerate depending on the location and severity of injury. Schwann cells (SCs) interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Schwann cells (SCs) recruit macrophages to the injury site through the expression of monocyte chemoattractant protein-1 and leukemia inhibitory factor, aiding in debris clearance following Wallerian degeneration.
2
Fibroblasts contribute to nerve repair by interacting with SCs and producing extracellular matrix molecules (ECMs), such as tenascin-C (TNC), which promotes SC migration via direct binding to SC-expressed β1 integrin.
3
Macrophage-derived microvesicles, specifically from M2 macrophages, promote SC proliferation and migration by upregulating nerve growth factor (NGF) and laminin, which has therapeutic implications for promoting axonal regeneration.

Research Summary

This review provides a comprehensive assessment of Schwann cell (SC) function post-peripheral nerve injury (PNI), focusing on SC interactions with macrophages and fibroblasts, which significantly influence SC behavior and nerve repair. The interplay between SCs, macrophages, and fibroblasts is crucial for debris elimination, axonal regeneration, and eventual myelination, highlighting the pro-regenerative capacity of the peripheral nervous system compared to the central nervous system. Clinical interventions leveraging SCs, such as modified nerve grafts and scaffolds, aim to enhance axonal regeneration and improve functional outcomes post-PNI, emphasizing the importance of understanding the timing of nerve repair and the factors influencing SC responses.

Practical Implications

Improved Nerve Repair Strategies

Understanding the specific interactions between Schwann cells, macrophages, and fibroblasts can lead to the development of targeted therapies to enhance nerve regeneration after injury.

Novel Therapeutic Targets

Identifying key molecules and signaling pathways involved in SC migration and function can reveal new targets for pharmacological interventions to promote nerve repair.

Enhanced Graft Design

Incorporating knowledge of cellular interactions into the design of nerve grafts and scaffolds can improve their effectiveness in promoting axonal regeneration and functional recovery.

Study Limitations

1
The precise mechanisms underlying inter- and intracellular changes in Schwann cells after PNI remain unclear.
2
The role of fibroblasts in nerve injury and regeneration, as well as in SC function, has not been extensively studied.
3
Further research is needed to fully elucidate the interactions between macrophages and SCs in PNI.

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