Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs

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 () and Tony Jun Huang ()
Additional contact information
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
Tony Jun Huang: Duke University

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-43239-6

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