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Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs

Author

Listed:
  • Ye He

    (Duke University)

  • Shujie Yang

    (Duke University)

  • Pengzhan Liu

    (Duke University)

  • Ke Li

    (Duke University)

  • Ke Jin

    (Duke University)

  • Ryan Becker

    (Duke University)

  • Jinxin Zhang

    (Duke University)

  • Chuanchuan Lin

    (Xinqiao Hospital)

  • Jianping Xia

    (Duke University)

  • Zhehan Ma

    (Duke University)

  • Zhiteng Ma

    (Duke University)

  • Ruoyu Zhong

    (Duke University)

  • Luke P. Lee

    (Brigham and Women’s Hospital
    University of California, Berkeley
    University of California, Berkeley
    Sungkyunkwan University)

  • Tony Jun Huang

    (Duke University)

Abstract

While mesenchymal stem cells (MSCs) have gained enormous attention due to their unique properties of self-renewal, colony formation, and differentiation potential, the MSC secretome has become attractive due to its roles in immunomodulation, anti-inflammatory activity, angiogenesis, and anti-apoptosis. However, the precise stimulation and efficient production of the MSC secretome for therapeutic applications are challenging problems to solve. Here, we report on Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs: AIMS. We create an acoustofluidic mechanobiological environment to form reproducible three-dimensional MSC aggregates, which produce the MSC secretome with high efficiency. We confirm the increased MSC secretome is due to improved cell-cell interactions using AIMS: the key mediator N-cadherin was up-regulated while functional blocking of N-cadherin resulted in no enhancement of the secretome. After being primed by IFN-γ, the secretome profile of the MSC aggregates contains more anti-inflammatory cytokines and can be used to inhibit the pro-inflammatory response of M1 phenotype macrophages, suppress T cell activation, and support B cell functions. As such, the MSC secretome can be modified for personalized secretome-based therapies. AIMS acts as a powerful tool for improving the MSC secretome and precisely tuning the secretory profile to develop new treatments in translational medicine.

Suggested Citation

  • Ye He & Shujie Yang & Pengzhan Liu & Ke Li & Ke Jin & Ryan Becker & Jinxin Zhang & Chuanchuan Lin & Jianping Xia & Zhehan Ma & Zhiteng Ma & Ruoyu Zhong & Luke P. Lee & Tony Jun Huang, 2023. "Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43239-6
    DOI: 10.1038/s41467-023-43239-6
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    References listed on IDEAS

    as
    1. Joseph Rufo & Peiran Zhang & Ruoyu Zhong & Luke P. Lee & Tony Jun Huang, 2022. "A sound approach to advancing healthcare systems: the future of biomedical acoustics," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    2. Michael Baudoin & Jean-Louis Thomas & Roudy Al Sahely & Jean-Claude Gerbedoen & Zhixiong Gong & Aude Sivery & Olivier Bou Matar & Nikolay Smagin & Peter Favreau & Alexis Vlandas, 2020. "Spatially selective manipulation of cells with single-beam acoustical tweezers," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    3. Amy Y. Clark & Karen E. Martin & José R. García & Christopher T. Johnson & Hannah S. Theriault & Woojin M. Han & Dennis W. Zhou & Edward A. Botchwey & Andrés J. García, 2020. "Integrin-specific hydrogels modulate transplanted human bone marrow-derived mesenchymal stem cell survival, engraftment, and reparative activities," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
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