Pyroptosis: candidate key targets for mesenchymal stem cell-derived exosomes for the treatment of bone-related diseases

Stem Cell Research & Therapy, 2025 · DOI: https://doi.org/10.1186/s13287-025-04167-y · Published: January 21, 2025

Regenerative Medicine Genetics Musculoskeletal Medicine

Simple Explanation

Bone-related diseases are a major cause of disability, with limited treatment options. This review explores how mesenchymal stem cell-derived exosomes (MSC-Exos) can regulate pyroptosis, a form of cell death that contributes to inflammation in bone diseases. MSCs have therapeutic potential, but challenges like immune response and cell survival exist. MSC-Exos offer a cell-free alternative, demonstrating more effective therapeutic effects. The review examines how MSC-Exos alleviate bone-related diseases by regulating pyroptosis. It explores potential therapeutic targets for these disorders, highlighting the anti-inflammatory, anti-death, and tissue repair properties of MSC-Exos.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Not specified

Key Findings

1
MSC-Exos have low immunogenicity, are more accessible, have improved preservation qualities, and potentially have low carcinogenic risks compared to MSCs.
2
MSC-Exos regulate pyroptosis through signaling pathways such as PI3K-AKT, YAP/β-catenin, NF-κB, and STAT3, and by regulating upstream targets like TRAF6, TXNIP, FOXO3, ELAVL1, and CMPK2.
3
MSC-Exos can inhibit the activation of caspase-11 and the expression of caspase-4 by delivering miR-203a-3p.2, reducing the secretion of IL-1β and IL-6, alleviating macrophage pyroptosis.

Research Summary

This review provides a comprehensive overview of how mesenchymal stem cell-derived exosomes (MSC-Exos) regulate pyroptosis to alleviate bone-related diseases. It highlights the potential of MSC-Exos as a therapeutic approach for conditions like osteoarthritis, rheumatoid arthritis, disc herniation, spinal cord injury, and osteoporosis. MSC-Exos have shown promising results in preclinical studies, demonstrating anti-inflammatory, anti-death, and tissue repair properties. They modulate the expression of key genes and proteins associated with pyroptosis, offering a new perspective for treating bone-related diseases. The review also discusses the challenges in translating MSC-Exos therapy from laboratory research to clinical application. It suggests the use of Artificial Intelligence (AI) to optimize the design, production, purification, and therapeutic application of MSC-Exos.

Practical Implications

Therapeutic Potential

MSC-Exos offer a promising therapeutic approach for various bone-related diseases by regulating pyroptosis and reducing inflammation.

Targeted Delivery

Exosomes can be used as targeted delivery carriers of proangiogenic and anti-inflammatory factors to enhance the intervention in the imbalance of pyroptosis.

Clinical Translation

Further research and clinical trials are needed to validate the therapeutic potential of MSC-Exos and develop standardized manufacturing practices and regulatory frameworks.

Study Limitations

1
Difficulties in large-scale exosome production, isolation, and purification.
2
Lack of highly specific identification approaches for exosomes.
3
Limited clinical efficacy data, with most applications remaining in preclinical research.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine