Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord
Abstract
:1. Introduction
2. Spinal Cord Injury and Promising Therapeutic Approaches for SCI Repair
3. Use of Schwann Cell Transplantation as a Promising Therapeutic Strategy for Injured Spinal Cord Repair
4. Exosomal Vesicles: A Next-Generation Cell-Derived Therapeutic Modality
5. Current Status of Exosomal Vesicle Use as a Therapy in Spinal Cord Injury Repair
6. Potential of Schwann Cell-Derived Exosomes (SCEVs) for SCI Repair
7. Limitations of SCEVs as a Therapeutic Modality for Nervous System Repair
8. Engineering Schwann Cell-Derived Exosomes for Maximizing Therapeutic Efficacy
9. Future Prospectives and Limitations of Schwann Cell-Derived Exosomes in Spinal Cord Injury Repair
Funding
Conflicts of Interest
References
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Aspect | SCEVs Benefit over SCs | SCEVs Limitations to SCs | Ref. |
---|---|---|---|
Delivery method | Ease of systemic administration; delivery of EVs is minimally invasive and amenable to repetitive dosing. | [79,80,81] | |
Crossing barrier | Smaller-size SCEVs will make it easier to overcome cell barriers and diffuse in the extracellular space. EVs can effectively cross the blood–brain or the blood–spinal cord barrier. | [82] | |
Targeted effect | The ability to engineer SCEV surfaces to design targeted delivery of specific protein or RNA cargo will allow for cell-specific targeting. | Ambiguity in identifying targeted recipient cells. Mechanism of SCEV recognition and specific uptake by target cells is unclear. | [83,84,85,86] |
Immunogenicity | Inherent advantages of EVs in terms of immune evasion will eliminate the need of using immune suppression following administration. | [73,87] | |
Circulation time and half-life | Short circulation time following systemic administration (mins to an hour) due to rapid removal by the immune system, which may result in only a transient biological effect. May require repeated dosing for persistent or long-term effect. | [86] | |
Zeta potential | Poor zeta potential, can lead to formation of unstable EV aggregates that may minimize efficacy, interfere with delivery, hinder with identification of optimal dosing, reduce circulation time, and induce an immune response. | [88] | |
Storage and shelf life | Long-term and simpler storage and shipping required compared to parent cells. | Alterations in the cargo consistency of EVs due to outward leakage of cargo content during storage. | [89] |
Manufacturing challenges | Additional processing steps required beyond cell isolation and culture. Yield limited by growth conditions and characteristics of parent cell. Lack of standardized protocols for isolating and purifying SCEVs. | [89] | |
Cost | Scalability and manufacturing greater than parent cell, increasing production cost. | [90] | |
Safety concerns | Enhanced safety profile. Lower tumorgenicity potential. Reduced risk of embolism. | [91,92] | |
Tool for therapeutic interventions | Versatile molecular cargo of coding and noncoding RNAs, proteins, and nucleic acids that can regulate cellular processes and mediate tissue repair. | [93,94,95,96,97] | |
Intercellular interactions | Lack of direct cell–axon association and guidance properties. Cannot directly replace lost neural cells. Cannot provide a structural substrate for repair like parent cells. | [60,98] | |
Regulatory approval | Associated with fewer ethical constraints compared to the therapeutic use of parent cells in people. | [79] |
SCI Model | SCEV Purification | EV Delivery | Dose | Outcomes | Reference |
---|---|---|---|---|---|
Mouse, level: T10, severe spinal cord crush injury. | Centrifugation: 1000× g for 10 min 10,000× g for 30 min Ultracentrifugation: 100,000× g for 1 h Washing with PBS buffer 100,000× g for 1 h | Three administrations a week for 4 weeks via tail vein injection after induction of SCI. | 250 µL of 0.1 μg/μL | Functional recovery accompanied by reduced CSPG deposition. | Pan et al., 2021 [149] |
Rat, level: T10, spinal cord contusion. Injury induced using fall of a 10 g rod from a height of 2.5 cm. | Centrifugation: 1000× g for 10 min 10,000× g for 30 min Ultracentrifugation: 100,000× g for 1 h Washing with PBS buffer 100,000× g for 1 h | Three administrations a week for 4 weeks via tail vein injection after induction of SCI. | 250 µL of 0.1 μg/μL | Increased autophagy, reduced apoptosis, decreased injury cavitation, axonal protection, and improved recovery of motor function. | Pan et al., 2022 [150] |
Rat, level: T10, spinal cord contusion. Injury induced using fall of a 8 g rod from a height of 4 cm. | Centrifugation: 1000× g for 10 min 1000× g for 20 min Filtration using a 0.22 μm filter Ultracentrifugation: 100,000× g for 70 min | Single administration via tail vein injection initiated at 30 min post SCI. | 100 µg | Attenuated tissue damage, reduced lesion size. Profound angiogenesis and improved BBB scores after SCI. | Huang et al., 2023 [116] |
Rat, level: T9, spinal cord clip compression. Injury induced using 30 g force using a vascular clip. | Centrifugation: 300× g for 5 min 2000× g for 20 min 10,000× g for 60 min Filtration using a 0.22 μm filter Ultracentrifugation: 110,000× g for 70 min | Daily administration via tail vein injection during the initial week after SCI followed by three injections per week until survival endpoint. | 500 μL of 0.1 mg | Reduced inflammation by alleviating oxidative stress. Increased mitophagy to minimize mitochondrial dysfunction. Reduced axonal damage and improvement in BBB scores. | Xu et al., 2023 [145] |
Rat, level: T10, spinal cord contusion. Injury induced using fall of a 10 g rod from a height of 2.5 cm. | Centrifugation: 300× g for 5 min 2000× g for 20 min 10,000× g for 60 min Filtration using a 0.22 μm filter Ultracentrifugation: 130,000× g for 70 min | Three administrations per week via tail vein injection, initiated at 30 min post SCI. | 50 µL (0.1 μg/μL) | Inhibited neuronal apoptosis, reduced inflammation, promoted M2 macrophage polarization, improved nerve conduction, bladder function, and BBB scores after SCI. | Ren et al., 2023 [143] |
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Ghosh, M.; Pearse, D.D. Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord. Int. J. Mol. Sci. 2023, 24, 17317. https://doi.org/10.3390/ijms242417317
Ghosh M, Pearse DD. Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord. International Journal of Molecular Sciences. 2023; 24(24):17317. https://doi.org/10.3390/ijms242417317
Chicago/Turabian StyleGhosh, Mousumi, and Damien D. Pearse. 2023. "Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord" International Journal of Molecular Sciences 24, no. 24: 17317. https://doi.org/10.3390/ijms242417317
APA StyleGhosh, M., & Pearse, D. D. (2023). Schwann Cell-Derived Exosomal Vesicles: A Promising Therapy for the Injured Spinal Cord. International Journal of Molecular Sciences, 24(24), 17317. https://doi.org/10.3390/ijms242417317