Exosomes: a promising microenvironment modulator for spinal cord injury treatment

Abstract

Spinal cord injury (SCI) remains a severely disabling disorder that impacts millions globally by causing irreversible damage to the nervous system. Although cell - based therapies have shown notable progress, the post - injury microenvironment presents significant obstacles that hinder the survival and effectiveness of implanted cells, ultimately limiting sustained functional restoration. Exosomes have emerged as a promising cell - free therapeutic alternative due to their stability, low immunogenicity, and ability to carry bioactive molecules such as proteins, microRNAs, and lipids. These vesicles can modulate the injured microenvironment, support neuroprotection, and facilitate repair. This review begins by discussing the pathological alterations that disrupt the microenvironment following SCI. The review then outlines the process of exosome formation and highlights their structural features. Furthermore, the review delves into the diverse cellular sources of exosomes and evaluates their therapeutic relevance in the context of SCI. Special attention is given to the multifaceted roles exosomes play in neuroprotection, such as reinforcing the blood - spinal cord barrier, stimulating axonal regeneration, promoting new blood vessel formation, suppressing programmed cell death in neurons, and modulating inflammatory responses. The synergistic use of exosomes in combination with biomaterials is also explored, with the aim of optimizing their therapeutic potential. Lastly, the review addresses the key obstacles that must be overcome to bring exosome - based treatments into clinical application and offers perspectives on future advancements in this evolving field. In summary, exosomes offer a novel and promising avenue for SCI intervention, holding considerable promise as an alternative to traditional therapeutic approaches.

Keywords: Exosomes; Mechanism; Microenvironment Modulator; Spinal Cord Injury.

Figure 1

Tissue imbalance of microenvironment after SCI, including demyelination and re - myelination, hemorrhage and ischemia, and scar formation. Created with BioRender.com.

Figure 2

Cellular imbalance of microenvironment after SCI, including neural death, activation of macrophages and microglia, and astrocyte reaction and proliferation. Created with BioRender.com.

Figure 3

Molecular imbalance of microenvironment after SCI, including cytokines and chemokine, neurotrophic factor, neurotransmitter, and extracellular matrix composition. TNF - α, Tumor necrosis factor - α. IL, Interleukin. GM - CSF, Granulocyte - macrophage colony stimulating factor. ILF, Leukocyte inhibitory factor. CXCL, C - X - C motif ligand. CXCR, C - X - C chemokine receptor. SDF - 1α, stromal cell - derived factor 1α. ICAM - 1, Intercellular adhesion molecule - 1. VCAM - 1, Vascular cell adhesion protein - 1. NGF, Nerve growth factor. Brain - derived neurotrophic factor. NT - 3, Neurotrophin - 3. CSPGs, Chondroitin sulfate proteoglycans. MMPs, Matrix metalloproteinases. Created with BioRender.com.

Figure 4

A timeline of landmark studies on exosome-based SCI therapies. Created with BioRender.com. Created with BioRender.com.

Figure 5

The biogenesis, structure and composition of exosomes. Created with BioRender.com.

Figure 6

Cell source of exosomes and its mechanism for modulating microenvironment after SCI. Created with BioRender.com.

Figure 7

Schematic diagram of exosomes combined with biomaterials for the treatment of SCI. Exosomes can be combined with hydrogel, 3D print biomaterials, and nanomaterials respectively to treat spinal cord injury. Created with BioRender.com.