What Is The Purpose Of Schwann Cells – Schwann cells (SC) have an important role in the peripheral nervous system. These cells are capable of supporting axons during homeostasis and after injury. However, mutations in genes related to the SC repair program or myelination cause SC dysfunction. Some neuropathies such as Charcot–Marie–Tooth (CMT) disease, diabetic neuropathy and Guillain–Barré syndrome show abnormal SC function and impaired regeneration processes. Therefore, there is a need to understand SCs-axon interactions and the neural environment in the context of homeostasis as well as post-injury and disease onset. Several neurotrophic factors, cytokines, and regulators of signaling pathways related to proliferation, survival, and regeneration are involved in this process. Preclinical studies focus on finding therapeutic targets for neuropathy and peripheral injury. To study the effects of new therapeutic targets, in vitro and in vivo modeling of neuropathy and peripheral nerve injury (PNI) is a useful tool. Additionally, several in vitro protocols have been designed using SC and neuronal 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 of somatic cells into SCs or SCs derived from pluripotent stem cells to produce functional SCs. This review will discuss the advantages of this system and the problems associated with it. Additionally, there are challenges in establishing adequate and reproducible protocols in vitro to recapitulate the improvements in SC-neuron interactions observed in vivo. Thus, we also address the repair mechanisms of SCs-axon interactions in the context of peripheral neuropathy and nerve injury (PNI) in vitro and in vivo. Finally, we summarize recent preclinical studies evaluating new transgenes, drugs, and compounds with translational potential into clinical studies.

The peripheral nervous system (PNS) is the part of the nervous system outside the brain and spinal cord. It plays a key role in providing information to the brain and from the brain to organs. Peripheral nerves are surrounded by glial cells called Schwann cells (SCs), which sometimes cover the axons with a myelin sheath, and are the main glial cell type in the PNS. They play an important role in the development, maintenance, function, and regeneration of peripheral nerves (Jessen et al., 2015). Myelinated SCs provide the myelin sheath on large axons, which is the insulating layer that forms around the nerve. This insulating sheath allows the transmission of action potentials along the axon quickly and efficiently. The PNS also contains non-myelinating SCs, called Remak cells, a class of SCs that form Remak bundles, which support small-caliber axons during homeostasis and after injury.

What Is The Purpose Of Schwann Cells

Myelinated or unmyelinated SCs play a very important role during nerve trauma. This event triggers several cellular and molecular events called Wallerian degeneration which causes the proximal nerve stump to regenerate while the distal nerve stump degenerates (Waller, 1985). SCs detach from axons, differentiate, proliferate, and acquire a repair phenotype ( Yang et al., 2008 ) ( Figure 1 ). Macrophages are recruited to injury sites to promote clearance of axonal debris and release cytokines and factors, thereby contributing to creating a favorable microenvironment ( Liu et al., 2019 ). Endothelial cells also participate in nerve regeneration through angiogenesis but also promote SC proliferation and migration ( Meng et al., 2022 ). Interestingly, endothelial cell-derived exosomes enhance and maintain the SC repair phenotype via miR199-5p and activation of the PI3K/AKT/PTEN signaling pathway ( Huang et al., 2023 ). Despite active nerve regeneration as noted above, in the context of disease, this process is constantly disrupted. Different from nerve trauma, which is usually caused by an acute injury at a specific site, peripheral neuropathy (PN) usually begins along the nerve and can become chronic over time. PN is usually caused by various genetic mutations, infections, autoimmune and metabolic manifestations, or side effects of chemotherapy. Such genetic diseases can spare SC but still cause abnormal myelin development (hypo- or hypermyelination). Therefore, the pathomechanism of PN varies based on several factors: SC involvement, and the nature or timing of myelin dysfunction.

Schwann Cell Interactions With Axons And Microvessels In Diabetic Neuropathy

Figure 1. The role of neurons and SCs in regeneration. Peripheral nerves are mainly formed by axons and SCs. SCs have an important role in nerve homeostasis and regeneration by supporting axons in several ways. Myelinated SCs on large axons (A). In response to injury, Wallerian degeneration occurs. SCs differentiate, proliferate, and initiate clearance of myelin debris. Macrophages migrate to the local area to take over phagocytosis of myelin and axonal debris and interact with other cells in the injured microenvironment (B). Differentiated SCs form Büngner bands and remyelinate axons. Several neurotrophic factors, cytokines, and exosomes are released from local cell populations that interact with axons. In this sequence, the axons begin to grow larger in an attempt to re-innervate the target organ (C). Successful reinnervation is the ultimate goal of nerve regeneration, but this is rarely achieved because it depends on several factors such as age, severity of injury, and distance from the cell body (D).

SCs are the main supporting cells in the peripheral nervous system. Whether with a myelinating or non-myelinating phenotype, SCs support axons during development and are essential for their function and maintenance. After nerve damage, SCs, called repair SCs, dedifferentiate and activate repair programs to support nerve regeneration ( Jessen and Mirsky, 2016 ). SCs act in the peripheral nervous system through several means, such as remyelination, direct release of neurotrophic factors, neuroprotection/axonoprotection and transfer of extracellular vesicles, iron, lactate and ribosomes (Figure 2). These mechanisms are critical for understanding the interactions between SCs and neurons during homeostasis but also after trauma or the onset of disease.

Figure 2. SCs support axons during development, homeostasis, and repair through several means. SC plasticity allows these cells to have an important participation in supporting axons during nerve development, maintenance, and regeneration. Several functions have been identified for SCs to enhance axonal regeneration following injury or disease onset. The main known functions are neurotrophic factors (NTFs) and cytokine release, remyelination, neuroprotection/axonoprotection, secretion of extracellular vesicles for cells or cell-axons. communication, and also the transport of lactate and ribosomes between the SC and the axon.

Myelination occurs during nervous system development and is maintained in neurological health. Efficient clearance of myelin debris following injury or disease is essential for regeneration to occur. SC repair is a local primary phagocytic cell, which breaks down its own myelin in a process called myelinophagy, which is regulated by the JNK/c-Jun pathway ( Gomez-Sanchez et al., 2015 ). SC repair also triggers a local innate immune response by releasing several cytokines. Specifically, this behavior is important for attracting and activating neutrophils and macrophages, the latter taking over the phagocytosis of axonal and myelin debris. SC repair guides axon regrowth to the target location by forming Büngner bands, and once aligned with the axon, begins remyelination. In chronic myelin dysfunction, the number and repair capacity of SCs decreases over time (Sulaiman and Gordon, 2009). Additionally, in some diseases, such as Charcot–Marie–Tooth disease (CMT) and chronic inflammatory demyelinating polyneuropathy, the constant cycle of demyelination and regeneration efforts forms a dysfunctional myelin layer, and forms concentric layers of SC processes and collagen around the axon. (Smith et al., 1980 Snider, 1994 Midroni and Bilbao, 1995).

Grant To Explore Schwann Cells’ Role In Oral Cancer Pain

It is well studied that SC repair supplies trophic factors to axons early in development to guide budding growth cones, and for maintenance and repair. Studies using neurotrophic factor knockout mice highlight the importance of these molecules because they exhibit lethal or dysfunctional phenotypes. For example, brain-derived neurotrophic factor heterozygous mice have impaired feeding behavior and abnormal locomotor activity (Kernie, 2000), whereas the knockout mouse phenotype shows loss of sensory and sympathetic neurons and dies within the first month of life (Crowley et al., 1994). Among the several trophic factors released by SC repair into axons are nerve growth factor (Bandtlow et al., 1987; Meyer et al., 1992), brain-derived growth factor (Meyer et al., 1992), ciliary neurotrophic factor (Meyer et al., 1992). al., 1992), vascular endothelial growth factor (Höke et al., 2006), hepatocyte growth factor (Höke et al., 2006), neurotrophin-3 (Sahenk et al., 2008), pleiotropin (Mi et al., 2007), and insulin-like growth factors (Syroid et al., 1999). Interestingly, non-myelinating and myelinating SCs show the release of different types of neurotrophic factors as some factors play a more important role than others depending on whether the nerve is primarily sensory or motor. For example, pleiotropins are essential for motor nerve regeneration while sensory nerves require nerve growth and brain-derived factors for regeneration ( Höke et al., 2006 ). These molecules can be released into the axon in two ways: via extracellular vesicles or as soluble factors not contained in the vesicles.

Nerve bodies in the spinal cord and dorsal root ganglia also depend on neurotrophic support from glia for survival, maintenance, and repair. SC-derived neurotrophic factors are delivered to the nerve bodies via retrograde axonal transport ( Davies, 1998 ) supporting nerve survival. In vitro studies using SC-conditioned media on motor neurons show that SC repair supports neuronal survival by providing neurotrophic factors to neurons (Bosch et al., 1988; Wu and Zhu, 1996).

There is little significant neuronal death in most peripheral neuropathies, with axons and myelin being most affected. On the other hand, after nerve injury, several morphological and molecular changes occur

What do schwann cells do, purpose of schwann cells, what are schwann cells, functions of schwann cells, what is the purpose of stem cells, location of schwann cells, what is the purpose of t cells, purpose of t cells, purpose of white blood cells, what is the purpose of white blood cells, what is the function of schwann cells, purpose of stem cells