Key Takeaways & Executive Findings
- •• Exosomes, as natural nanocarriers, offer a promising cell-free therapeutic approach for spinal cord injury (SCI) repair due to their stability, biocompatibility, and low immunogenicity. • The review systematically summarizes exosome isolation techniques, including ultracentrifugation, size-based methods, and microfluidics, highlighting the need for scalable production for clinical translation. • Various exosome sources (e.g., mesenchymal stem cells) and administration routes are discussed, with evidence showing their potential to modulate inflammation, inhibit apoptosis, and promote axonal regeneration. • Combining exosomes with other strategies, such as biomaterial scaffolds or drugs, may enhance therapeutic efficacy, but challenges like standardization and large-scale production remain.
Abstract
Spinal cord injury (SCI) is a catastrophic injury to the central nervous system (CNS) that can lead to sensory and motor dysfunction, which seriously affects patients’ quality of life and imposes a major economic burden on society. The pathological process of SCI is divided into primary and secondary injury, and secondary injury is a cascade of amplified responses triggered by the primary injury. Due to the complexity of the pathological mechanisms of SCI, there is no clear and effective treatment strategy in clinical practice. Exosomes, which are extracellular vesicles of endoplasmic origin with a diameter of 30–150 nm, play a critical role in intercellular communication and have become an ideal vehicle for drug delivery. A growing body of evidence suggests that exosomes have great potential for repairing SCI. In this review, we introduce exosome preparation, functions, and administration routes. In addition, we summarize the effect and mechanism by which various exosomes repair SCI and review the efficacy of exosomes in combination with other strategies to repair SCI. Finally, the challenges and prospects of the use of exosomes to repair SCI are described.
1. Introduction
SCI is a catastrophic injury to the CNS that can lead to sensory and motor dysfunction and is characterized by a high rate of disability and mortality [1, 2]. Approximately 10.4–83 per 1 million people suffer from SCI each year worldwide. Furthermore, the morbidity and mortality rates are increasing each year. SCI still imposes significant costs on society and presents several challenges to the medical community [3]. After SCI, a series of pathophysiological changes occur at the lesion site, including inflammatory response and neuronal apoptosis, which are followed by the formation of cavities and scars, resulting in the inhibition of axonal regeneration [4]. Unfortunately, regeneration after SCI is extremely weak due to the low plasticity of the CNS and limited neuronal regeneration. Currently, there is no effective method to completely repair the function of the spinal cord after SCI [5].
Exosomes, which are extracellular vesicles of endoplasmic origin with a diameters of 30–150 nm, are secreted by cells [6]. Exosomes contains various biologically active molecules, including nucleic acids and proteins, which play a crucial role in intercellular communication [7, 8]. Importantly, exosomes show good stability, biocompatibility, biological barrier permeability, and low immunogenicity, which supports their use in the repair of tissue damage [9–11]. Furthermore, exosomes can carry new functional proteins through genetically engineered cells [12, 13]. In addition, exosomes can also be used as carriers of small molecules or nucleic acids to target drugs to specific types of cells or tissues [14–16]. Thus, exosomes are not only a potential tool for exploring the mechanism of SCI but may also be an important substance for repairing SCI in the future [17–19]. Consequently, in this article, we describe the preparation, functions, administration routes mechanism, and challenges of various exosomes in the treatment of SCI.
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Tong Yu, Li-Li Yang, Ying Zhou, Min-Fei Wu, Jian-Hang Jiao (2026). Exosome-mediated repair of spinal cord injury: a promising therapeutic strategy. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-023-03614-y
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Frequently Asked Questions
What are exosomes and how are they relevant to spinal cord injury repair?
Exosomes are small extracellular vesicles (30-150 nm) that mediate intercellular communication by transferring bioactive molecules. They show promise in SCI repair due to their stability, biocompatibility, and ability to modulate inflammation and promote regeneration.
What are the main challenges in using exosomes for SCI treatment?
Challenges include low extraction efficiency and purity, lack of standardized production methods, and the need for large-scale manufacturing for clinical applications. Additionally, optimal administration routes and dosing need to be established.
How are exosomes isolated for research and potential clinical use?
Common isolation techniques include ultrahigh-speed centrifugation, size-based isolation, polymer precipitation, immunoaffinity capture, and microfluidic methods. Each has trade-offs in yield and purity, and further optimization is needed.
Can exosomes be combined with other therapies to enhance SCI repair?
Yes, the review discusses combining exosomes with other strategies such as biomaterial scaffolds or drugs, which may synergistically improve outcomes by providing structural support and sustained release of therapeutic factors.
What is the potential of exosomes as drug delivery vehicles for SCI?
Exosomes can be engineered to carry small molecules, nucleic acids, or proteins, and can target specific cells or tissues, making them ideal drug delivery vehicles for SCI treatment, potentially improving efficacy and reducing side effects.
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