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Cited by 54Extracellular vesicles in diseaseMesenchymal stem cell researchTissue Engineering and Regenerative Medicine

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Bolstering the secretion and bioactivities of umbilical cord MSC-derived extracellular vesicles with 3D culture and priming in chemically defined media

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Kim, Jun Yong, Rhim, Won-Kyu, Cha, Seung-Gyu, Woo, Jiwon, Lee, Joo Youn, Park, Chun Gwon, Han, Dong Keun·2022·Nano Convergence
DOI 10.1186/s40580-022-00349-zPMC PMC9761620
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Abstract

Human mesenchymal stem cells (hMSCs)-derived extracellular vesicles (EVs) have been known to possess the features of the origin cell with nano size and have shown therapeutic potentials for regenerative medicine in recent studies as alternatives for cell-based therapies. However, extremely low production yield, unknown effects derived from serum impurities, and relatively low bioactivities on doses must be overcome for translational applications. As several reports have demonstrated the tunability of secretion and bioactivities of EVs, herein, we introduced three-dimensional (3D) culture and cell priming approaches for MSCs in serum-free chemically defined media to exclude side effects from serum-derived impurities. Aggregates (spheroids) with 3D culture dramatically enhanced secretion of EVs about 6.7 times more than cells with two-dimensional (2D) culture, and altered surface compositions. Further modulation with cell priming with the combination of TNF-α and IFN-γ (TI) facilitated the production of EVs about 1.4 times more than cells without priming (9.4 times more than cells with 2D culture without priming), and bioactivities of EVs related to tissue regenerations. Interestingly, unlike changing 2D to 3D culture, TI priming altered internal cytokines of MSC-derived EVs. Through simulating characteristics of EVs with bioinformatics analysis, the regeneration-relative properties such as angiogenesis, wound healing, anti-inflammation, anti-apoptosis, and anti-fibrosis, for three different types of EVs were comparatively analyzed using cell-based assays. The present study demonstrated that a combinatory strategy, 3D cultures and priming MSCs in chemically defined media, provided the optimum environments to maximize secretion and regeneration-related bioactivities of MSC-derived EVs without impurities for future translational applications.

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  • EVs are proficient at carrying diverse biomolecules, such as proteins, mRNAs, and non-coding RNAs, to target cells.

    “EVs are proficient at carrying diverse biomolecules, such as proteins, messenger RNAs (mRNAs), and non-coding RNAs, to target cells [45–47].”

    From Extracellular vesicles as nanotheranostic platforms for targeted neurological disorder interventions (2024) · cites this paper as [47]

    The Introduction says EVs transfer proteins and miRNA, a non-coding RNA, to adjacent cells. It does not mention messenger RNA, so that specific cargo in the citing sentence is not supported by our copy. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Metadata

Authors
Kim, J. Y., Rhim, W.-K., Cha, S.-G., Woo, J., Lee, J. Y., Park, C. G., & Han, D. K.
Affiliations
  • CHA University (KR)
  • Sungkyunkwan University (KR)
Corresponding author
Han, Dong Keun
ORCID
Venue
Nano Convergence
Publisher
Springer Science and Business Media LLC
Published
2022-12-19
Volume
9
Issue
1
Pages
57-57
ISSN
2196-5404 (ISSN-L)
DOI
10.1186/s40580-022-00349-z
PMC
PMC9761620
OpenAlex
W4312067548
Cited by
54
References
6
Citations by year
2026: 10 · 2025: 10 · 2024: 22 · 2023: 12
FWCI
3.59
Type
journal article
Language
en
Open access
Licence
Locations
  • Nano Convergence (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Ministry of Science and ICT, South Korea (2020R1A2B5B03002344, 2018M3A9E2024579, 202011A05-05)
  • Ministry of Education (2022R1I1A1A01068486)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
mesenchymal stem cells, extracellular vesicles, 3D cell culture, spheroids, cell priming, chemically defined medium, serum-free culture, EV secretion, angiogenesis, wound healing, anti-inflammatory activity, apoptosis inhibition, anti-fibrosis, tissue regeneration, cell therapy

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