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Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Mesenchymal stem cells (MSCs) are used for tissue regeneration due to their wide differentiation capacity and anti-inflammatory effects. Extracellular vesicles (EVs) derived from MSCs are also known for their regenerative effects as they contain nucleic acids, proteins, lipids, and cytokines similar to those of parental cells. There are several studies on the use of MSCs or EVs for tissue regeneration. However, the combinatorial effect of human MSCs (hMSCs) and EVs is not clear. In this study, we investigated the combinatorial effect of hMSCs and EVs on cartilage regeneration via co-encapsulation in a hyaluronic-acid (HA)-based hydrogel.

Methods:

A methacrylic-acid-based HA hydrogel was prepared to encapsulate hMSCs and EVs in hydrogels. Through in vitro and in vivo analyses, we investigated the chondrogenic potential of the HA hydrogel-encapsulated with hMSCs and EVs.

Results:

Co-encapsulation of hMSCs with EVs in the HA hydrogel increased the chondrogenic differentiation of hMSCs and regeneration of damaged cartilage tissue compared with that of the HA hydrogel loaded with hMSCs only.

Conclusion:

Co-encapsulation of hMSCs and EVs in the HA hydrogel effectively enhances cartilage tissue regeneration due to the combinatorial therapeutic effect of hMSCs and EVs. Thus, in addition to cartilage tissue regeneration for the treatment of osteoarthritis, this approach would be a useful strategy to improve other types of tissue regeneration.

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Acknowledgements

This work was funded by the Korean government (MSIT, MOE, and MOHW) (NRF-2022R1A2C3004850, NRF-2020R1I1A1A01074331, NRF-2019M3A9H1032376, and 21C0703L1).

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Correspondence to Yoshie Arai or Soo-Hong Lee.

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The study protocol was approved by the institutional review board of Dongguk University (IRB No. DUIH2020-03-012-022). Informed consent was confirmed by the IRB. The animal studies were performed after receiving approval of the Institutional Animal Care and Use Committee (IACUC) in Dongguk University (IACUC approval no. IACUC-2021-018-2).

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Cho, W.J., Ahn, J., Lee, M. et al. Combinatorial Effect of Mesenchymal Stem Cells and Extracellular Vesicles in a Hydrogel on Cartilage Regeneration. Tissue Eng Regen Med 20, 143–154 (2023). https://doi.org/10.1007/s13770-022-00509-6

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