Enhancing Mesenchymal Stromal Cell Potency: Inflammatory Licensing via Mechanotransduction

Area of Science:

• Biomedical Engineering
• Cell Therapy Manufacturing
• Immunomodulation

Background:

• Mesenchymal stromal cells (MSC) mature and gain immune regulatory functions at injury sites.
• Inflammatory signals and biomechanical forces are known stimuli for MSC maturation.
• Current methods often rely on pro-inflammatory cytokines for MSC conditioning.

Purpose of the Study:

• To investigate if wall shear stress (WSS) can enhance MSC immunomodulatory potential.
• To determine if WSS-mediated maturation is independent of pro-inflammatory cytokines.
• To assess the scalability and reproducibility of WSS conditioning for MSC.

Main Methods:

• Exposing human adipose and bone marrow MSC to varying WSS levels using a scalable platform.
• Quantifying immunomodulatory markers like prostaglandin E2 (PGE2) and indoleamine 2,3 dioxygenase 1 (IDO1).
• Assessing the suppression of pro-inflammatory cytokines (TNF-α, IFN-γ) by activated immune cells.
• Analyzing cell viability, yield, identity, and gene expression via transcriptome analysis.

Main Results:

• WSS exposure enhanced MSC immunomodulatory capacity in a dose-dependent manner.
• WSS conditioning increased PGE2 and IDO1 production and suppressed TNF-α and IFN-γ.
• This effect was observed in both adipose and bone marrow MSC without compromising cell viability or identity.
• Transcriptome analysis revealed significant changes in immunomodulatory gene expression.

Conclusions:

• Mechanotransduction via WSS is a viable, scalable method to enhance MSC immunomodulatory function.
• WSS conditioning offers an alternative to pro-inflammatory cytokines for MSC pre-conditioning.
• This approach represents a novel manufacturing strategy for improving cell-based therapies.