Therapeutic potential of small extracellular vesicles derived from mesenchymal stem cells for spinal cord and nerve injury

Front. Cell Dev. Biol., 2023 · DOI: 10.3389/fcell.2023.1151357 · Published: March 22, 2023

Simple Explanation

Neural diseases, including traumatic injuries, can lead to motor, sensory, and autonomic function losses, and current treatments are limited. Mesenchymal stem cells (MSCs) have been explored for their anti-inflammatory and regenerative properties. However, conflicting outcomes and limitations like heterogeneity and ethical concerns have hindered their use. Extracellular vesicles (EVs), containing nucleic acids, proteins, and lipids, have emerged as a promising alternative. EVs play roles in immune regulation, inflammation reduction, and cell communication, potentially overcoming limitations associated with MSCs like size issues and immunogenicity. This review explores the therapeutic potential of EVs for treating neural pathologies, discussing their mechanisms of action and future clinical applications. It aims to provide a comprehensive overview of EVs as a novel therapeutic source in regenerative medicine.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Small EVs, particularly those derived from adipose tissue-MSCs (ADMSCs), offer therapeutic potential for improving neural structure after injury. They promote nerve regeneration and reduce risks associated with MSC transplantation, such as immune response and tumorigenesis.
2
Small EVs contain various miRNAs that play essential regulatory roles during axonal growth and inflammation through various signaling pathways. These miRNAs can be delivered to specific cells, influencing nerve regeneration and modulating the immune response.
3
Bioengineering improvements are needed to address identified clinical and commercial limitations of small EVs. This includes optimizing production processes, standardization of small EVs generation, and determining potency and molecular activity.

Research Summary

This review discusses the therapeutic potential of small extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) for treating spinal cord and nerve injuries. It highlights the limitations of traditional MSC therapies and introduces EVs as a novel alternative due to their roles in immune regulation, inflammation reduction, and cell-to-cell communication. The review details the isolation and characterization of small EVs, emphasizing methods like ultracentrifugation, ultrafiltration, and size-exclusion chromatography. It also explores the differences between MSCs and small EVs, particularly those derived from adipose tissue, noting the advantages of small EVs in terms of stability and reduced risk of immune rejection. The authors conclude that while small EVs offer promise for improved management of neural injuries, challenges related to tissue source, isolation, purification, and amplification must be addressed. They call for standardized procedures and clinical trials to establish the effectiveness and safety of small EVs in humans.

Practical Implications

Therapeutic Development

Small EVs represent a promising therapeutic avenue for neural injuries, potentially offering advantages over traditional MSC therapies.

Clinical Translation

Addressing challenges in EV isolation, purification, and standardization is crucial for translating EV-based therapies to clinical applications.

Drug Delivery Systems

Small EVs can be used for drug delivery or as paracrine signaling components in stem cell- or progenitor cell-based therapies.

Study Limitations

1
Variability in cell culture conditions and small EVs isolation methods among laboratories.
2
Lack of standardized, scalable, and cost-effective production systems for clinical use.
3
Challenges in developing a reliable potency assay for MSC-EVs due to their complex characteristics.

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