Effects of ECM proteins (laminin, fibronectin, and type IV collagen) on the biological behavior of Schwann cells and their roles in the process of remyelination after peripheral nerve injury

Abstract

Introduction: It is important to note that complete myelination and formation of myelinated fibers are essential for functional nerve regeneration after peripheral nerve injury (PNI). However, suboptimal myelin regeneration is common and can hinder ideal nerve regeneration. Therefore, it is important to closely monitor and support myelin regeneration in patients with PNI to achieve optimal outcomes.Methods: This study analyzed the effects of three extracellular matrix (ECM) proteins on Schwann cells (SCs) in the nerve regeneration environment, including their adhesion, proliferation, and migration. The study also explored the use of composite sodium alginate hydrogel neural scaffolds with ECM components and investigated the effects of ECM proteins on remyelination following peripheral nerve injury.Results: The results showed that laminin (LN), fibronectin (FN), and collagen Ⅳ (type IV Col) promoted the early adhesion of SCs in 2-dimensional culture but the ratios of early cell adhesion were quite different and the maintenance of cells’ morphology by different ECM proteins were significantly different. In transwell experiment, the ability of LN and FN to induce the migration of SCs was obviously higher than that of type IV Col. An vitro co-culture model of SCs and dorsal root ganglia (DRG) neurons showed that LN promoted the transition of SCs to a myelinated state and the maturation of the myelin sheath, and increased the thickness of neurofilaments. Animal experiments showed that LN had superior effects in promoting myelin sheath formation, axon repair, and reaching an ideal G-ratio after injury compared to FN and Col IV. The situation of gastrocnemius atrophy was significantly better in the LN group. Notably, the thickness of the regenerated myelin sheaths in the type IV Col group was the thickest.Conclusion: In this experiment, we analyzed and compared the effects of LN, FN, and type IV Col on the biological behavior of SCs and their effects on remyelination after PNI and further clarified their unique roles in the process of remyelination. Further research is necessary to explore the underlying mechanisms.

Acellular spinal cord scaffold containing quercetin-encapsulated nanoparticles plays an anti-inflammatory role in functional recovery from spinal cord injury in rats

“…DAPI and H&E staining con rmed the absence of cellular components and the preservation of tissue structure within the scaffold. Immuno uorescence staining further con rmed the presence of important ECM components, such as LM, FN, and Col IV, which play crucial roles in nerve regeneration environment, including their proliferation, migration, and adhesion (Yu et al, 2023). The DNA content of the scaffold was signi cantly reduced after decellularization, indicating the successful removal of cellular remnants.…”

Exploring miR‐21 as a key regulator in two distinct approaches of bone marrow stromal cells differentiation into Schwann‐like cells

“…IGF can affect the differentiation of MSCs into SCs by regulating multiple cellular signaling pathways (Khodabakhsh et al, 2021). Additionally, extracellular matrix proteins such as laminin, fibronectin, and collagen provide support for the growth and differentiation of SCs (Guan et al, 2023;Yu et al, 2023). Zhou et al demonstrated that exosomes derived from SCs, particularly those carrying biologically active molecules, such as miRNAs, proteins, and lipids, play an important role in promoting the differentiation of MSCs into SCs.…”

Interactions between Schwann cell and extracellular matrix in peripheral nerve regeneration

“…These materials can bridge the gap in injured nerves, provide guidance for regenerating axons, and support a protective microenvironment, thereby facilitating better cell growth and reducing the probability of nerve tumor formation. The closer the microstructure of a good nerve scaffold conduit material is to natural tissue, the greater the success rate of regeneration transplantation ( 10 , 29 , 75–77 ).…”

“…The team led by Peng Yu found that laminin (LN), fibronectin (FN), and type IV collagen (IV-Col) possess the ability to promote early adhesion of SCs in 2D culture. However, there are significant differences in the proportion of early cell adhesion, and the expression levels required for maintaining cell morphology vary markedly with different ECM proteins ( 10 ). Stephanie J Armstrong’s earlier study on the impact of ECM molecules on SC adhesion and proliferation on poly(3-hydroxybutyrate) (PHB) nerve conduit material yielded similar findings, highlighting the role of LN in enhancing synaptic growth by activating NF-kappaB in SCs ( 91 , 92 ).…”

“…The ECM is a complex molecular network synthesized and released into the extracellular space by cells residing in tissues or organs ( 9 ). Its main components include collagen, proteoglycans/glycosaminoglycans, elastin, laminin, fibronectin, etc., providing structural support and attachment sites for cells ( 10 ). Schwann cells, as the primary glial cells in the peripheral nervous system, play various crucial roles and are considered the gold standard in cell therapy for peripheral nerve injuries ( 7 , 11 ).…”