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Continuous Isolation of Stem-Cell-Derived Extracellular Vesicles (SC-EVs) by Recycled Magnetic Beads in Microfluidic Channels

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Abstract

Stem cells produce nanosized particles known as extracellular vesicles (SC-EVs), which therapeutically affect stem cells. EVs are more abundantly produced, exhibit better stability, and possess lower immune rejection rates than stem cells. However, the traditional methods of isolating EVs, such as ultracentrifugation, possess limitations that require a complex process and consume more time. Moreover, it is difficult to isolate specific EVs that have target surface proteins that affect regenerative effects. To address these limitations, a new dual-mode horseshoe-shaped orifice micromixer (DM-HOMM) chip that can bind antibody-conjugated micromagnetic beads and SC-EVs and sequentially elute specific SC-EVs on the beads using an eluent was developed. For effective elution from the microbead-SC-EV complex, four types of eluents were used to control pH and ionic strength between antibodies and surface proteins in EVs. In addition, we investigated the reusability of antibody-conjugated micromagnetic beads. The beads indicated identical binding efficiencies between the antibodies and specific SC-EVs for three repeated cycles using the dual-mode chip. CD63+ EVs collected by the chip exhibited higher cell viability and regeneration effects than untreated and total EVs. This SC-EVs’ isolation method possesses the potential for targeted therapeutic applications and enhanced regenerative effects.

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Data availability

The authors declare that the data supporting the findings of this study are available within the paper and its Supplementary Information files.

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Acknowledgements

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020M3A9I4039045, No. 2021R1A2C3011254, and No. 2023M3A9I4010261) and the Technology Innovation Program (20008829) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

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Authors and Affiliations

  1. School of Mechanical Engineering, Yonsei University, 50, Yonsei-ro, Seoul, 03722, Republic of Korea

    Haeun Yu, Jaejeung Kim, Jianning Yu, Kyung-A Hyun, Sunyoung Park & Hyo-Il Jung

  2. Department of Otorhinolaryngology, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seoul, 03722, Republic of Korea

    Jae-Yol Lim & Yeo-Jun Yoon

  3. Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University, 1 Yonseidae-gil, Wonju, 26493, Republic of Korea

    Jianning Yu

  4. The DABOM Inc., Seoul, Republic of Korea

    Sunyoung Park & Hyo-Il Jung

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  1. Haeun Yu
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Correspondence to Sunyoung Park or Hyo-Il Jung.

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Yu, H., Kim, J., Yu, J. et al. Continuous Isolation of Stem-Cell-Derived Extracellular Vesicles (SC-EVs) by Recycled Magnetic Beads in Microfluidic Channels. BioChip J 17, 468–477 (2023). https://doi.org/10.1007/s13206-023-00122-2

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