Key Takeaways & Executive Findings
- •• Exosomes derived from various cell types exhibit potent neuroprotective effects in preclinical SCI models, promoting functional recovery. • The mechanisms of exosome action include neurogenesis, angiogenesis, preservation of the blood-spinal cord barrier, anti-apoptosis, and anti-inflammatory modulation. • Exosome cargo, including miRNAs and proteins, modulates key signaling pathways involved in secondary injury cascade. • Despite challenges, exosome-based therapies hold promise for translational application in SCI, offering targeted delivery and reduced side effects.
Abstract
Patients with spinal cord injury (SCI) have permanent devastating motor and sensory disabilities. Secondary SCI is known for its complex progression and presents with sophisticated aberrant inflammation, vascular changes, and secondary cellular dysfunction, which aggravate the primary damage. Since their initial discovery, the potent neuroprotective effects and powerful delivery abilities of exosomes (Exos) have been reported in different research fields, including SCI. In this study, we summarize therapeutic advances related to the application of Exos in preclinical animal studies. Subsequently, we discuss the mechanisms of action of Exos derived from diverse cell types, including neurogenesis, angiogenesis, blood–spinal cord barrier preservation, anti-apoptosis, and anti-inflammatory potential. We also evaluate the relationship between the Exo delivery cargo and signaling pathways. Finally, we discuss the challenges and advantages of using Exos to offer innovative insights regarding the development of efficient clinical strategies for SCI.
1. Introduction
Spinal cord injury (SCI) is one of the most serious neurological disorders, with a global incidence of 1.2–5.8 and 0.2–13.0 cases per 100 000 population in developed and developing countries, respectively [1–6]. Approximately 90% of SCIs are caused by traumatic events, such as traffic accidents, falls, or acts of violence [6]. SCI results in enduring impairments, including paralysis, sensory loss, and long-term complications, including muscle atrophy, joint deformities, infections, atelectasis, pneumonia, venous thromboembolism, dysphagia, chronic pain, pressure ulcer, and psychological distress such as depression [7, 8], thereby accounting for a substantial proportion of the worldwide injury burden of lost productivity and high healthcare costs [5].
Currently, no effective treatment is available to mitigate long-term functional impairments attributed to SCI. Available therapies, such as anti-inflammatory medications, have limited efficacy since they are rapidly eliminated by cerebrospinal fluid, and their bioactivity is diminished [9, 10]. This is partly due to a limited understanding of the intricate pathophysiological processes that occur after SCI and a lack of safe and efficient instruments to regulate the already known therapeutic targets [11].
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Yueying Li, Wenqi Luo, Chuikai Meng, Kaiyuan Shi, Rui Gu, Shusen Cui (2026). Exosomes as promising bioactive materials in the treatment of spinal cord injury. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-024-03952-5
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Frequently Asked Questions
What are exosomes and how are they relevant to spinal cord injury treatment?
Exosomes are small extracellular vesicles that mediate intercellular communication by transferring bioactive molecules. In SCI, they have shown neuroprotective effects, promoting functional recovery by modulating inflammation, apoptosis, and promoting regeneration.
What are the main mechanisms by which exosomes exert therapeutic effects in SCI?
Exosomes derived from various cell types exert effects through promoting neurogenesis, angiogenesis, preserving the blood-spinal cord barrier, inhibiting apoptosis, and modulating inflammatory responses.
What are the challenges in translating exosome-based therapies for SCI to clinical use?
Challenges include standardization of exosome isolation and characterization, ensuring targeted delivery to the injured spinal cord, potential immunogenicity, and scalability of production under good manufacturing practices.
What is the significance of exosome cargo in SCI treatment?
Exosome cargo, including microRNAs, proteins, and lipids, can modulate key signaling pathways involved in secondary injury, offering a multifaceted approach to counteract the complex pathophysiology of SCI.
What is the future outlook for exosome-based therapies in SCI?
With ongoing research, exosome-based therapies hold promise as a novel strategy for SCI, potentially offering targeted, efficient, and safer alternatives to current treatments, but further preclinical and clinical studies are needed.
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