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Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy

  • Review Article
  • Published:
Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background

Exosomes, nano-sized vesicles ranging between 30 and 150 nm secreted by human cells, play a pivotal role in long-range intercellular communication and have attracted significant attention in the field of regenerative medicine. Nevertheless, their limited productivity and cost-effectiveness pose challenges for clinical applications. These issues have recently been addressed by cell-derived nanovesicles (CDNs), which are physically synthesized exosome-mimetic nanovesicles from parent cells, as a promising alternative to exosomes. CDNs exhibit structural, physical, and biological properties similar to exosomes, containing intracellular protein and genetic components encapsulated by the cell plasma membrane. These characteristics allow CDNs to be used as regenerative medicine and therapeutics on their own, or as a drug delivery system.

Methods

The paper reviews diverse methods for CDN synthesis, current analysis techniques, and presents engineering strategies to improve lesion targeting efficiency and/or therapeutic efficacy.

Results

CDNs, with their properties similar to those of exosomes, offer a cost-effective and highly productive alternative due to their non-living biomaterial nature, nano-size, and readiness for use, allowing them to overcome several limitations of conventional cell therapy methods.

Conclusion

Ongoing research and enhancement of CDNs engineering, along with comprehensive safety assessments and stability analysis, exhibit vast potential to advance regenerative medicine by enabling the development of efficient therapeutic interventions.

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Fig. 1
Fig. 2
Fig. 3

© 2015 PLOS), NTA, DLS, and AFM (Reprinted with permission from Ridolfi et al. [86], Copyright © 2020 American Chemical Society)

Fig. 4

© 2022 Springer Nature), B MALDI-TOF/MS and coupled TLC and MALDI-TOF/MS (Reprinted with permission from Lobasso et al. [96], Copyright © 2021 Frontiers), and C fluorescence-based lipid analysis (Reprinted with permission from Cha et al. [101], Copyright © 2023 American Chemical Society)

Fig. 5

© 2020 John Wiley & Sons, Inc. B CDNs were synthesized from IONP-treated hMSCs resulting in enhanced growth factor release. Magnetic attraction was employed to recruit CDNs to the spinal cord injury site. Reprinted with permission from Kim et al. [65], Copyright © 2018 American Chemical Society. C C6 cell membrane fragments were extruded with tumor targeting (T7c) peptides to synthesize T7c-incorporating CDNs. Anti-miRNA-21 oligonucleotide, modified with cholesterol, was sequentially loaded through hydrophobic interaction. Reprinted with permission from Lee et al. [109], Copyright © 2022 John Wiley & Sons, Inc. D CDNs were extruded from HEK293 cells engineered to express an EGFR-binding domain for cancer targeting. The CDNs were fused with photosensitizer-loaded liposomes for cancer therapy. Reprinted with permission from Shin et al. [110], Copyright © 2023 The Korean Society of Industrial and Engineering Chemistry

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Data availability

The datasets used and/or analyzed during the present study are available from the corresponding author on reasonable request.

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Acknowledgements

This study received funding from (i) the National Research Foundation of Korea (NRF), funded by the Korean government (MSIT) (2021R1C1C1011015, 2021K1A3A1A74099704, and RS-2023-00213691); (ii) the Brain Korea 21 PLUS Project for the Department of Biological Science of Sookmyung Women’s University; (iii) Sookmyung Women’s University Research Grants (1-2103-2002 and 1-2203-2025); and National Research Foundation of Korea (NRF) (2021R1C1C1011015, 2021K1A3A1A74099704, RS-2023–00213691).

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  1. Hye-Jeong Jang, Kyu-Sik Shim, Jinah Lee have contributed equally to this work.

Authors and Affiliations

  1. Department of Systems Biotechnology, Chung-Ang University, Anseong-Si, Gyeonggi-Do, 17546, Republic of Korea

    Hye-Jeong Jang, Seong-Jun Kang & Jeong-Kee Yoon

  2. Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Severance Hospital, Yonsei University College of Medicine, Seoul, 03722, Republic of Korea

    Kyu-Sik Shim & Wooyeol Baek

  3. Department of Biological Science, Research Institute of Women’s Health, Brain Korea 21 Project, Sookmyung Women’s University, Seoul, 04310, Republic of Korea

    Jinah Lee, Joo Hyeon Park, Young Min Shin & Jung Bok Lee

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Jang, HJ., Shim, KS., Lee, J. et al. Engineering of Cell Derived-Nanovesicle as an Alternative to Exosome Therapy. Tissue Eng Regen Med 21, 1–19 (2024). https://doi.org/10.1007/s13770-023-00610-4

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