Substance P enhances mesenchymal stem cells-mediated immune modulation.

Area of Science:

• Immunology
• Cell Biology
• Regenerative Medicine

Background:

• Mesenchymal stem cells (MSCs) lose therapeutic activity after long-term ex vivo culture due to senescence.
• Substance P (SP), a neuropeptide, activates MSCs, enhancing proliferation, migration, and cytokine secretion.
• Maintaining MSC therapeutic potential is crucial for clinical applications.

Purpose of the Study:

• To investigate SP's ability to restore the immunosuppressive function of late-passage MSCs.
• To determine the mechanism by which SP affects MSC immune modulation.
• To assess the potential of SP-treated MSCs for enhancing therapeutic activity.

Main Methods:

• Assessed T cell activity and IL-2 secretion in CD4+ Jurkat and primary T cells co-cultured with MSCs.
• Utilized NK1 receptor blocker and TGF-beta signaling inhibitors to elucidate SP's mechanism.
• Measured TGF-β1 and IL-10 secretion in SP-treated MSC cultures.
• Confirmed SP's effect via direct cell-cell contact co-culture.

Main Results:

• Long-term culture reduced MSC immunosuppressive function, which was restored by SP treatment.
• SP-induced restoration of MSC function was blocked by NK1 receptor inhibition.
• SP treatment increased TGF-β1 secretion in late-passage MSCs, but not IL-10.
• SP-mediated enhancement of MSC immunosuppression involves the TGF-beta signaling pathway.

Conclusions:

• SP pretreatment can recover the immunosuppressive function of late-passage MSCs.
• SP potentiates TGF-β1 secretion, enhancing the therapeutic activity of ex vivo expanded MSCs.
• SP holds promise for improving the clinical efficacy of MSC-based therapies.