Acoustofluidic Interfaces for the Mechanobiological Secretome of MSCs

Area of Science:

• Biotechnology
• Regenerative Medicine
• Cell Biology

Background:

• Mesenchymal stem cells (MSCs) possess therapeutic potential, but their secretome production requires optimization for clinical use.
• The MSC secretome offers immunomodulatory, anti-inflammatory, and pro-angiogenic benefits.
• Current methods for efficient MSC secretome production and precise stimulation are challenging.

Purpose of the Study:

• To develop an acoustofluidic system (AIMS) for efficient and reproducible production of MSC secretome.
• To investigate the role of cell-cell interactions in AIMS-mediated secretome enhancement.
• To evaluate the therapeutic potential of AIMS-generated secretome, particularly after IFN-γ priming.

Main Methods:

• Creation of an acoustofluidic mechanobiological environment to form 3D MSC aggregates.
• Analysis of N-cadherin expression to confirm the role of cell-cell interactions.
• Priming MSC aggregates with IFN-γ to modulate secretome profile.
• Assessment of the immunomodulatory effects of the secretome on macrophages, T cells, and B cells.

Main Results:

• AIMS successfully generated reproducible 3D MSC aggregates, significantly increasing secretome production.
• Enhanced secretome production was attributed to increased cell-cell interactions, evidenced by N-cadherin upregulation.
• IFN-γ primed secretome exhibited potent anti-inflammatory properties, inhibiting M1 macrophage activation and T cell proliferation while supporting B cell function.
• AIMS demonstrated its capability to precisely tune the secretome's therapeutic profile.

Conclusions:

• AIMS is an effective tool for enhancing MSC secretome production and optimizing its therapeutic properties.
• The system facilitates the development of personalized, secretome-based therapies.
• AIMS holds significant promise for advancing translational medicine through improved cell-based therapeutics.