Schwann cells (SCs) are the primary glial cells of the Peripheral Nervous System (PNS), which insulate and provide protection and nutrients to the axons. Technological and experimental advances in neuroscience, focusing on the biology of SCs, their interactions with other cells, and their role in the pathogenesis of various diseases, have paved the way for exploring new treatment strategies that aim to harness the direct protective or causative properties of SCs in neurological disorders. SCs express cytokines, chemokines, neurotrophic growth factors, matrix metalloproteinases, extracellular matrix proteins, and extracellular vesicles, which promote the inherent potential of the injured neurons to survive and accelerate axonal elongation. The ability of SCs to support the development and functioning of neurons is lost in certain hereditary, autoimmune, metabolic, traumatic, and toxic conditions, suggesting their role in specific neurological diseases. Thus, targeting, modifying, and replacing SC strategies, as well as utilizing SC-derived factors and exosomes, have been considered novel therapeutic opportunities for neuropathological conditions. Preclinical and clinical data have demonstrated that SCs and SC-derived factors can serve as viable cell therapy for reconstructing the local tissue microenvironment and promoting nerve anatomical and functional recovery in both peripheral and central nerve injury repair, as well as in peripheral neuropathies. However, despite the promising successes of genetic engineering of SCs, which are now in preclinical and clinical trials, improving tactics to obtain ‘repair’ SCs and their products from different sources is the key goal for future clinical success. Finally, further development of innovative therapeutic approaches to target and modify SC survival and function in vivo is also urgently needed.

Schwann cells (SCs) are the primary glial cells of the PNS, which insulate and provide protection and nutrients to the axons. Technological and experimental advances in neuroscience, focusing on the biology of SCs, their interactions with other cells, and their role in the pathogenesis of various diseases, have paved the way for exploring new treatment strategies that aim to harness the direct protective or causative properties of SCs in neurological disorders. SCs express cytokines, chemokines, neurotrophic growth factors, matrix metalloproteinases, extracellular matrix proteins, and extracellular vesicles, which promote the inherent potential of the injured neurons to survive and accelerate axonal elongation. The ability of SCs to support the development and functioning of neurons is lost in certain hereditary, autoimmune, metabolic, traumatic, and toxic conditions, suggesting their role in specific neurological diseases. Thus, targeting, modifying, and replacing SC strategies, as well as utilizing SC-derived factors and exosomes, have been considered novel therapeutic opportunities for neuropathological conditions. Pre-clinical and clinical data have demonstrated that SCs and SC-derived factors can serve as a viable cell therapy for reconstructing the local tissue microenvironment and promoting nerve anatomical and functional recovery in both peripheral and central nerve injury repair, as well as in peripheral neuropathies. However, despite the promising successes of genetic engineering of SCs, which are now in pre-clinical and clinical trials, improving tactics to obtain ‘repair’ SCs and their products from different sources is the key goal for future clinical success. Finally, further development of innovative therapeutic approaches to target and modify SC survival and function in vivo is also urgently needed.