Therapy For Spinal Cord Injury Research Articles

Mechanism of effect and therapeutic potential of NLRP3 inflammasome in spinal cord injury.

Spinal cord injury (SCI) is a serious and disabling central nervous system injury that can trigger various neuropathological conditions, resulting in neuronal damage and release of various pro-inflammatory mediators, leading to neurological dysfunction. Currently, surgical decompression, drugs and rehabilitation are primarily used to relieve symptoms and improve endogenous repair mechanisms; however, they cannot directly promote nerve regeneration and functional recovery. SCI can be divided into primary and secondary injuries. Secondary injury is key to determining the severity of injury, whereas inflammation and cell death are important pathological mechanisms in the process of secondary SCI. The activation of the inflammasome complex is thought to be a necessary step in neuro-inflammation and a key trigger for neuronal death. The NLRP3 inflammasome is a cytoplasmic multiprotein complex that is considered an important factor in the development of SCI. Once the NLRP3 inflammasome is activated after SCI, NLRP3 nucleates the assembly of an inflammasome, leading to caspase 1-mediated proteolytic activation of the interleukin-1β (IL-1β) family of cytokines, and induces an inflammatory, pyroptotic cell death. Inhibition of inflammasomes can effectively inhibit inflammation and cell death in the body and promote the recovery of nerve function after SCI. Therefore, inhibition of NLRP3 inflammasome activation may be a promising approach for the treatment of SCI. In this review, we describe the current understanding of NLRP3 inflammasome activation in SCI pathogenesis and its subsequent impact on SCI and summarize drugs and other potential inhibitors based on NLRP3 inflammasome regulation. The objective of this study was to emphasize the role of the NLRP3 inflammasome in SCI, and provide a new therapeutic strategy and theoretical basis for targeting the NLRP3 inflammasome as a therapy for SCI.

Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies.

Spinal cord injury (SCI) is a severely debilitating neurological condition that often results in significant functional impairment and is associated with poor long-term prognosis. Edema, oxidative stress, inflammatory responses, and cell death are the primary factors contributing to secondary injury following spinal cord damage. Ubiquitination is a crucial intracellular mechanism for protein regulation that has garnered significant attention as a therapeutic target in a variety of diseases. Numerous studies have shown that ubiquitination plays a key role in modulating processes such as inflammatory responses, apoptosis, and nerve regeneration following SCI, thereby influencing injury repair. Accordingly, targeting ubiquitination has the potential for mitigating harmful inflammatory responses, inhibiting dysregulated programmed cell death, and protecting the integrity of the blood-spinal cord barrier, thereby providing a novel therapeutic strategy for SCI. In this review, we discuss the role of ubiquitination and its potential as a therapeutic target in SCI, aiming to offer a foundation for developing ubiquitination-targeted therapies for this condition.

Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury.

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have emerged as a promising therapeutic strategy for spinal cord injury (SCI). These nanosized vesicles possess unique properties such as low immunogenicity and the ability to cross biological barriers, making them ideal carriers for delivering bioactive molecules to injured tissues. MSC-EVs have been demonstrated to exert multiple beneficial effects in SCI, including reducing inflammation, promoting neuroprotection, and enhancing axonal regeneration. Recent studies have delved into the molecular mechanisms underlying MSC-EV-mediated therapeutic effects. Exosomal microRNAs (miRNAs) have been identified as key regulators of various cellular processes involved in SCI pathogenesis and repair. These miRNAs can influence inflammation, oxidative stress, and apoptosis by modulating gene expression. This review summarized the current state of MSC-EV-based therapies for SCI, highlighting the underlying mechanisms and potential clinical applications. We discussed the challenges and limitations of translating these therapies into clinical practice, such as inconsistent EV production, complex cargo composition, and the need for targeted delivery strategies. Future research should focus on optimizing EV production and characterization, identifying key therapeutic miRNAs, and developing innovative delivery systems to maximize the therapeutic potential of MSC-EVs in SCI.

Activities of Daily Living in a Iranian Man With Cervical Spinal Cord Injury Based on the Model of Human Occupation

Background and Objectives: Since all aspects of occupational performance are affected by cervical spinal cord injury (SCI), one of the goals of occupational therapy for these clients is to restore the abilities and routines necessary for independence in activities of daily living (ADL). The model of human occupation (MOHO) seems to help occupational therapists develop a framework for clinical reasoning about the living conditions of people with cervical SCI emphasizing the interaction between volition, habituation, and performance capacity. This study aims to investigate the use of MOHO in occupational therapy for cervical SCI and focuses on the significance of comprehending and adjusting to these specific needs to improve their participation in purposeful daily activities leading to occupational adaptation. Case Presentation: The focus of this study is on a 26-year-old man who experienced a cervical SCI at the C6 level due to a diving accident. He exhibits varying degrees of motor and sensory deficits, characterized by partial upper extremity function and complete loss of function in the lower extremities. The client expresses a strong desire to develop skills for safe and effective transfers, the need for strategies that promote community reintegration and social interaction, and adaptive strategies and utilize assistive devices that will enable him to perform ADLs with greater independence. Conclusion: Because in a person with cervical SCI, values and interests, internalized roles, and performance capacities are affected by impairment, designing a program based on the MOHO will help occupational therapists perform more effectively.

Pharmacological Network Analysis of the Functions and Mechanism of Quercetin From Jisuikang (JSK) in Spinal Cord Injury (SCI).

Neuroinflammation, especially microglia/macrophage activation, is a hallmark of spinal cord injury (SCI). Jisuikang (JSK) is a clinical experiential Chinese herbal formula for SCI therapy containing Huangqi (Astragali Radix), Danggui (Angelica sinensis Radix), Chishao (Paeoniae Radix Rubra), Dilong (earthworm, Pheretima aspergillum), Chuanxiong (Chuanxiong Rhizoma), Taoren (Persicae Seman) and Honghua (Carthami Flos). Eighteen active ingredients in 6 herbs of JSK were found to be correlated with inflammation, spinal injury and other diseases. These 18 active ingredients target 5464 genes according to the PubChem database. Through comparing differentially expressed genes between SCI and normal samples using GSE datasets, 50 hub genes were identified. These hub-genes were enriched in oxidative stress response and inflammation response. The herb-compound-target, herb-compound-signalling and compound-target-signalling networks were generated and quercetin was identified as the hub compound. A concentration of 25 μM quercetin showed no cytotoxicity but significantly protected microglial cells from LPS-induced inhibition of cell viability. LPS stimulation elevated the levels of iNOS, IL-1β and TNF-α but decreased IL-10 levels, whereas quercetin significantly attenuated LPS-induced alterations in these factors. Moreover, quercetin targeted gene, IL1R1 was reduced by quercetin as predicted. Overexpression of IL1R1 further increased LPS-induced inflammation, which could be partly reversed by quercetin treatment. Invivo, quercetin improved histopathological alterations, inflammation and promoted M2 macrophage polarisation post-injury, whereas IL1R1 overexpression partially attenuated the beneficial effects of quercetin on the rat SCI model. Collectively, quercetin, the main ingredient compound of JSK, protects against LPS-induced cell viability inhibition and cellular inflammation, which could be partially attenuated by IL1R1 overexpression.

A biomimetic injectable chitosan/alginate hydrogel biocopmosites encapsulating selenium- folic acid nanoparticles for regeneration of spinal cord injury: An in vitro study.

Spinal cord injury (SCI) poses significant challenges to regenerative medicine due to its limited self-repair capabilities. In this study, we engineered a biomimetic injectable hydrogel using modified chitosan and alginate biopolymers encapsulating selenium-folic acid nanoparticles (Se-FA NPs) to facilitate SCI regeneration. The hydrogel exhibited a unique porous structure attributed to the incorporation of nanofiber fragments, enhancing its biocompatibility and bioactivity. Through a series of in vitro evaluations, including cell viability assays, proliferation studies, gene expression analysis, we assessed the hydrogel's cytocompatibility and its potential for supporting neural cell growth. Our results demonstrate the promising efficacy of the hydrogel in providing a conducive microenvironment for neural tissue regeneration. Moreover, the sustained release of Se-FA NPs from the hydrogel system offers neuroprotective, antioxidative, and anti-inflammatory benefits crucial for SCI therapy. Overall, our biomimetic hydrogel biocomposites hold great potential as a therapeutic strategy for promoting spinal cord regeneration, highlighting their significance in advancing the field of regenerative medicine.

Ezrin, a novel marker of ependymal cells, can be used to demonstrate their proliferation regulation after spinal cord injury in mice

Ependymal cells (EpCs), as a potential stem cell niche, have gained interest for their potential in vivo stem cell therapy for spinal cord injury (SCI). Heterogeneity of spinal EpCs may contribute to differences in the ability of spinal EpCs to proliferate, differentiate and transition after injury, while there is limited understanding of the regulation of these events. Our research found that ezrin (Ezr) was expressed highly in EpCs of the spinal cord, and its upregulation rapidly occurred after injury (6 h). It remained consistently highly expressed in proliferating EpCs, this occurs before pathological accumulation of it occurs in other glial and immune-related cells. Differential expression of Ezr, Arg3, Pvalb, Ccnd1, and Gmpr characterized distinct responses of EpCs to injury activity. Also, we uncovered the dynamic regulatory behavior of immature EpCs after injury. In contrast to constitutive expression in parenchymal tissues, injury factors upregulated guanosine monophosphate reductase (Gmpr) in arrested EpCs, unveiling a distinctive mechanism to regulate proliferation in EpCs following spinal cord injury.

Resveratrol Enhances the Efficacy of Combined BM-MSCs Therapy for Rat Spinal Cord Injury via Modulation of the Sirt-1/NF-κB Signaling Pathway.

Spinal cord injury (SCI) represents a severe trauma to the central nervous system, resulting in significant disability and imposing heavy burdens on families and society. Pathophysiological changes following SCI often trigger secondary injuries that complicate treatment. Bone marrow mesenchymal stem cells (BM-MSCs) have become a focal point of research due to their multifunctionality and self-renewal capabilities; however, their survival and neuroprotective functions are compromised in inflammatory environments. Resveratrol, known for its anti-inflammatory, anti-aging, and anti-oxidative stress properties, has been extensively studied. This research focuses on the anti-inflammatory effects of resveratrol post-SCI and its combined application with BM-MSCs to treat rat spinal cord injuries, exploring both efficacy and mechanisms. In vivo experiments investigated changes in the Sirt-1 signaling pathway post-SCI, while in vitro studies examined the effects of resveratrol on BM-MSCs under inflammatory conditions. The assessment included recovery of motor function, neuronal survival, and apoptosis in SCI rats treated with resveratrol alone or in combination with BM-MSCs. Findings reveal a correlation between Sirt-1 and inflammation signaling pathways post-injury. Resveratrol significantly enhanced the survival and efficacy of BM-MSCs in inflammatory environments by upregulating Sirt-1 and downregulating NF-κB and other inflammatory markers, thereby reducing apoptosis. Combined treatment with resveratrol and BM-MSCs showed superior outcomes in motor function recovery and neuronal survival compared to treatment with BM-MSCs alone. This study offers a novel therapeutic strategy for SCI, enhancing stem cell survival and function through modulation of the Sirt-1/NF-κB pathway, providing a theoretical and experimental foundation for clinical applications.

Innovative Strategies in Regenerative Medicine: Bridging Science and Clinical Practice

Regenerative medicine is a rapidly advancing field to revolutionize healthcare by offering innovative solutions for repairing or replacing damaged tissues and organs. By addressing significant challenges associated with conventional therapies—such as the shortage of donor organs and complications related to immune rejection—regenerative medicine provides a hopeful alternative for patients suffering from chronic diseases and injuries. This review outlines the urgent need for regenerative medicine to tackle prevalent issues like chronic conditions, organ scarcity, and injury recovery through approaches like stem cell therapy and tissue engineering. Key therapies currently available in the market, such as Carticel and Celution, utilize both autologous and allogeneic cells to promote healing and tissue regeneration. Recent breakthroughs showcase the transformative potential of regenerative medicine, with notable successes including stem cell therapies for spinal cord injuries, 3D-printed skin grafts for burn victims, and the development of lab-grown organs. These advancements highlight regenerative medicine's capability to enhance patient outcomes significantly. Looking ahead, the future of regenerative medicine lies in the personalization of therapies, advanced biomaterials, and cutting-edge technologies like 3D bioprinting. These innovations will enable the creation of complex and functional tissues tailored to individual patients. As research continues to progress, regenerative medicine holds the promise of offering long-term, transformative solutions for a wide range of medical conditions..

Screening of orthopedic medicines identifies raloxifene hydrochloride as a novel ferroptosis inhibitor for spinal cord injury therapy

Spinal cord injury (SCI) is a severe condition that can lead to irreversible central nervous system damage. Spinal cord injury patients frequently present with coexisting orthopedic conditions, and many of them also have underlying bone and joint diseases. Recent studies have identified ferroptosis as a significant contributor that exacerbates the progression of spinal cord injury. This study conducted a screening in common orthopedic medications, which includes anti-osteoporosis agents and calcium supplements, in order to identify potential ferroptosis inhibitors and investigate their therapeutic effects on spinal cord injury. Among the 8 drugs screened, raloxifene hydrochloride was found to significantly inhibit ferroptosis induced by RSL3 in neural cells. Subsequent studies confirmed its inhibitory effect on ferroptosis both in vitro and in vivo. It was also demonstrated that Nrf2 inhibitor Brusatol could reverse the anti-ferroptotic effect of Raloxifene hydrochloride in neural cells in vitro as well as its therapeutic effect on SCI in vivo, suggesting its inhibitory effect on ferroptosis is through Nrf2. This study identifies a novel ferroptosis inhibitor among orthopedic medicines and also confirms the therapeutic effect of Raloxifene hydrochloride on SCI. The results of the current study may provide reference for the clinical administration of SCI.

Injectable alginate chitosan hydrogel as a promising bioengineered therapy for acute spinal cord injury

Dealing with spinal cord injuries presents problematic due to multiple secondary mechanisms. Beyond primary concerns like paralysis and disability, complications including urinary, gastrointestinal, cardiac, and respiratory disorders, along with substantial economic burdens may occur. Limited research focuses on modeling and treating contusion and compression injuries. Tissue engineering emerges as an innovative treatment, targeting lesion pathophysiology. This study was evaluated implanting injectable biomaterials into injury-induced cavity before glial scar formation, avoiding tissue incisions and minimizing further damage. The efficacy of injectable alginate/thiolated chitosan hydrogel was investigated for acute spinal cord injury induced by Vanický method in Wistar rats. Three days post-injury, hydrogel was administrated through microinjection after laminectomy. After 60 days, the hydrogel group demonstrated notable motor function enhancement compared to the control by the BBB locomotor test (P < 0.05). However, no statistically significant differences were observed in MRI assessment concerning lesion severity. Stereological and histopathological evaluations revealed a reduction in vacuole volume and the presence of axon profiles within the scaffold (P < 0.05), alongside reduced infiltration of inflammatory and Gitter cells in the hydrogel group, although the latter was not statistically significant compared to the control. Thiolated chitosan/ alginate hydrogel implantation may be regarded as a promising treatment to enhance motor function by restraining destructive processes post-acute spinal cord injury.

Letter to the Editor Regarding “Exploring the Landscape of Hydrogel Therapy for Spinal Cord Injury: A Bibliometric and Visual Analysis (1991–2023)”

Letter to the Editor Regarding “Exploring the Landscape of Hydrogel Therapy for Spinal Cord Injury: A Bibliometric and Visual Analysis (1991–2023)”

Regenerative medicine for spinal cord injury using induced pluripotent stem cells: from animals to humans.

Spinal cord injury (SCI) results in permanent neurological dysfunction and neuropathic pain. To address this pathology, we recently conducted a clinical study in which we transplanted neural precursor cells (NPCs) derived from human induced pluripotent stem cells into patients during the subacute phase of SCI. One of the therapeutic mechanisms of cell transplantation is the formation of synaptic connections with the host's neural tissues, which we demonstrated using a chemogenetic tool. In addition, we have developed innovative strategies to enhance the effectiveness of cell transplantation through gene therapy. Moreover, our current study is focused on developing cell therapy for chronic SCI, a more challenging pathology characterized by the formation of cavities and scar tissue. In such situations, transplanting NPCs with neurogenic properties could effectively penetrate scar tissue and form functional synapses with the host neurons. To improve the outcomes of cell transplantation alone, we have found that incorporating rehabilitation is beneficial. In animal models of SCI, we have established an effective rehabilitative training program in which NPCs were transplanted during the chronic phase. Robotic rehabilitation has demonstrated improvements in gait ability and trunk function in clinical situations. Therefore, regenerative medicine shows promise for chronic SCI, particularly when rehabilitation strategies are incorporated.

Generation of self-renewing neuromesodermal progenitors with neuronal and skeletal muscle bipotential from human embryonic stem cells

Progress has been made in generating spinal cord and trunk derivatives from neuromesodermal progenitors (NMPs). However, maintaining the self-renewal of NMPs invitro remains a challenge. In this study, we developed a cocktail of small molecules and growth factors that induces human embryonic stem cells to produce self-renewing NMPs (srNMPs) under chemically defined conditions. These srNMPs maintain the state of neuromesodermal progenitors in prolonged culture and have the potential to generate mesodermal cells and neurons, even at the single-cell level. Additionally, suspended srNMP aggregates can spontaneously differentiate into all tissue types of early embryonic trunks. Furthermore, transplanted srNMP-derived muscle satellite cells or progenitors of motor neurons were integrated into skeletal muscle or the spinal cord, respectively, and contributed to regeneration in mouse models. In summary, srNMPs hold great promise for applications in developmental biology and as renewable cell sources for cell therapy for trunk and spinal cord injuries.

Restorative Treatments for Cervical Spinal Cord Injury, a Narrative Review.

A narrative review. To summarize relevant data from representative studies investigating upper limb restorative therapies for cervical spinal cord injury. Cervical spinal cord injury (SCI) is a debilitating condition resulting in tetraplegia, lifelong disability, and reduced quality of life. Given the dependence of all activities on hand function, patients with tetraplegia rank regaining hand function as one of their highest priorities. Recovery from cervical SCI is heterogeneous and often incomplete; currently, various novel therapies are under investigation to improve neurological function and eventually better quality of life in patients with tetraplegia. In this article, a narrative literature review was performed to identify treatment options targeting the restoration of function in patients with cervical SCI. Studies were included from available literature based on the availability of clinical data and whether they are applicable to restoration of arm and hand function in patients with cervical SCI. We describe relevant studies including indications and outcomes with a focus on arm and hand function. Different treatment modalities described include nerve transfers, tendon transfers, spinal cord stimulation, functional electrical stimulation, non-invasive brain stimulation, brain-machine interfaces and neuroprosthetics, stem cell therapy, and immunotherapy. As the authors' institution leads one of the largest clinical trials on nerve transfers for cervical SCI, we also describe how patients undergoing nerve transfers are managed and followed at our center. While complete recovery from cervical spinal cord injury may not be possible, novel therapies aimed at the restoration of upper limb motor function have made significant progress toward the realization of complete recovery.

The Application of Biomaterial-Based Spinal Cord Tissue Engineering.

Advancements in biomaterial-based spinal cord tissue engineering technology have profoundly influenced regenerative medicine, providing innovative solutions for both spinal cord organoid development and engineered spinal cord injury (SCI) repair. In spinal cord organoids, biomaterials offer a supportive microenvironment that mimics the natural extracellular matrix, facilitating cell differentiation and organization and advancing the understanding of spinal cord development and pathophysiology. Furthermore, biomaterials are essential in constructing engineered spinal cords for SCI repair. The incorporation of biomaterials with growth factors, fabrication of ordered scaffold structures, and artificial spinal cord assemblies are critical insights for SCI to ensure structural integrity, enhance cell viability, and promote neural regeneration in transplantation. In summary, this review summarizes the contribution of biomaterials to the spinal cord organoids progression and discusses strategies for biomaterial-based spinal cord engineering in SCI therapy. These achievements underscore the transformative potential of biomaterials to improve treatment options for SCI and accelerate future clinical applications.

Extracellular vesicles: Unlocking new therapies for spinal cord injury

Extracellular vesicles: Unlocking new therapies for spinal cord injury

Alterations in Endogenous Stem Cell Populations in the Acute Phase of Blast-Induced Spinal Cord Injury.

Blast-induced spinal cord injury (bSCI) is prevalent among military populations and frequently leads to irreversible spinal cord tissue damage that manifests as sensorimotor and autonomic nervous system dysfunction. Clinical recovery from bSCI has been proven to be multifactorial, as it is heavily dependent on the function of numerous cell populations in the tissue environment, as well as extensive ongoing inflammatory processes. This varied recovery process is thought to be due to irreversible spinal cord damage after 72 hours post-injury. Stem cell therapy for spinal cord injuries has long been investigated due to these cells' proliferative nature, ability to enhance neuro-regeneration, neuroprotection, remyelination of axons, and modulation of the immune and inflammatory responses. Therefore, this study hypothesizes that the impaired function after injury is due to a lack of specific ectoderm and neural stem cell population activity at the injury site. This study aimed to elucidate changes in endogenous stem cell patterns by evaluating immunohistochemical staining densities of various stem cell markers using a preclinical thoracolumbar bSCI model. Analysis was performed 24-, 48-, and 72 hours following blast exposure. Behavior tests to assess sensory and mechanical functions were also performed. The following Cluster of differentiation (CD) markers CD105, CD45, CD133, and Vimentin, Nanog homebox (NANOG), and sex determining region Y HMG-box 2 (SOX2) positive cell populations were significantly elevated with trending increases in Octamer-binding transcription factor 4 (OCT4) in the thoracolumbar region of spinal cord tissue at 72 hours following bSCI (p < 0.05). Behavior analyses showed significant decreases in paw withdrawal thresholds in the hind limbs and changes in locomotion at 48- and 72 hours post-injury (p < 0.05). The significant increase in mesenchymal, pluripotent, and neural stem cell populations within the thoracolumbar region post-injury suggests that migratory patterns of stem cell populations are likely altered in response to bSCI. Behavioral deficits were consistent with those experienced by military personnel, such as increased pain-like behavior, reduced proprioception and coordination, and increased anxiety-like behavior post-bSCI, which underlines the translational capabilities of this model. While further research is vital to understand better the intrinsic and synergistic chemical and mechanical factors driving the migration of stem cells after traumatic injury, increased endogenous stem cell populations at the injury site indicate that stem cell-based treatments in patients suffering from bSCI could prove beneficial.

Advancements and mechanisms of stem cell-based therapies for spinal cord injury in animals.

Spinal cord injury (SCI) is a neurodegenerative disorder of the central nervous system that can lead to permanent loss of sensation and voluntary movement beyond the affected area. Extensive preclinical and clinical trials have been conducted to evaluate the safety and effectiveness of stem cells for the treatment of various central nervous system diseases or disorders, including SCI. However, several challenges hinder nerve cell regeneration in the injured spinal cord, such as extensive cell loss, limited neural cell regeneration capacity, axonal disruption, and the presence of growth-inhibiting molecules, particularly astroglial scarring or glial scars at the injury site in chronic cases. These obstacles pose significant challenges for physicians in restoring normal motor and sensory nerve function in both humans and animals following SCI. This review focuses on SCI pathogenesis, the mechanisms underlying the therapeutic potential of mesenchymal stem cells in SCI, and the potential of stem cell-based therapies as promising avenues for treatment. This review article also included relevant preclinical and clinical data from animal studies.

Therapeutic Potential of Mesenchymal Stem Cell-Derived Exosomes in Spinal Cord Injury.

Spinal cord injury (SCI) can lead to severe motor and sensory dysfunction, with a high rate of disability and mortality. Due to the complicated pathological process of SCI, there is no effective clinical treatment strategy at present. Although mesenchymal stem cells (MSCs) are effective in the treatment of SCI, their application is limited by factors such as low survival rate, cell dedifferentiation, tumorigenesis, blood-brain barrier, and immune rejection. Fortunately, there is growing evidence that most of the biological and therapeutic effects of MSCs may be mediated by the release of paracrine factors, which are extracellular vesicles called exosomes. Exosomes are small endosomal vesicles with bilaminar membranes that have recently been recognized as key mediators for communication between cells and tissues through the transfer of proteins, lipids, nucleic acids, cytokines, and growth factors. Mesenchymal stem cell-derived exosomes (MSC-exos) play a critical role in SCI repair by promoting angiogenesis and axonal growth, regulating inflammation and immune response, inhibiting apoptosis, and maintaining the integrity of the blood-spinal cord barrier. Furthermore, they can be used to transport genetic material or drugs to target cells, and their relatively small size allows them to permeate the blood-brain barrier. Studies have demonstrated that some exosomal miRNAs derived from MSCs play a significant role in the treatment of SCI. In this review, we summarize recent research advances in MSC-exos and exosomal miRNAs in SCI therapy to better understand this emerging cell-free therapeutic strategy and discuss the advantages and challenges of MSC-exos in future clinical applications.