Tetraspanin 4 Mediates Cholesterol-Dependent Exosome Membrane Protection from Cryodamage
Exosomes, nanosized extracellular vesicles carrying proteins, lipids, and nucleic acids, hold great potential in therapeutic applications. Cryopreservation, a widely used method for their preservation and transport, often causes irreversible damage. Understanding the molecular mechanisms underlying biomembrane resistance to cryodamage is crucial for advancing cryopreservation techniques. In this study, we find that tetraspanin 4 (TSPAN4) and other tetraspanin family proteins play an essential role in protecting exosomes from cryodamage, likely due to their role in cholesterol binding and membrane microdomain formation. Furthermore, we engineered TSPAN4-loaded exosomes, which demonstrated enhanced cryoprotection while maintaining a similar protein composition and uptake efficiency compared to wild-type exosomes. Our novel cryopreservation strategy, which does not rely on external agents, offers a promising approach for advancing the clinical translation of exosomes as therapeutic agents.
Authors
- Yiling Wen (ORCID: https://orcid.org/0009-0001-7225-2149)
- Catherine C. L. Wong (ORCID: https://orcid.org/0000-0001-7270-980X)
- Pin Gao (ORCID: https://orcid.org/0000-0002-7691-8569)
- Xia Zheng
- Rui Ji (ORCID: https://orcid.org/0000-0003-2920-5766)
- Hongli Wang (ORCID: https://orcid.org/0009-0000-4755-624X)
- Wenmin Tian (ORCID: https://orcid.org/0009-0008-9754-2792)
- Jianjun Wang (ORCID: https://orcid.org/0000-0002-1704-9922)
- Zhang Liu (ORCID: https://orcid.org/0000-0001-8433-6289)
- Yong Li (ORCID: https://orcid.org/0000-0002-0330-657X)
- Chen Yang (ORCID: https://orcid.org/0000-0002-4841-9412)
- Dongxue Shi
Institutions
- Chinese Academy of Sciences (CN)
- Peking University (CN)
- Peking Union Medical College Hospital (CN)
- Clinical Research Institute (US)
- Peking University First Hospital (CN)
- Technical Institute of Physics and Chemistry (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Nano Letters
- Published
- 2025-05-19
- DOI
- https://doi.org/10.1021/acs.nanolett.5c00572
- Citations
- 3
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- National Key Research and Development Program of China