Proinflammatory Effect of Mesenchymal Stem Cells From Patients With Multiple Sclerosis: Potential Modulation Targets.

Area of Science:

• Immunology
• Cellular Therapy
• Neuroscience

Background:

• Mesenchymal stem cells (MSCs) are explored for multiple sclerosis (MS) treatment.
• MSCs from MS patients may exhibit reduced immunomodulatory capacity compared to healthy controls (HCs).

Purpose of the Study:

• To compare immunomodulatory effects of MSCs from MS patients versus HCs on autologous immune cells.
• To identify molecular targets influencing MSC immunomodulation in MS.

Main Methods:

• Bone marrow-derived MSCs and peripheral blood mononuclear cells (PBMCs) from MS patients and HCs.
• Flow cytometry to assess T-cell cytokine expression (IL-17, IFN-γ, GM-CSF) in monoculture and co-culture.
• Multiplex array/ELISA for cytokine analysis and RNA-seq for gene expression profiling of MSCs.

Main Results:

• HC MSCs suppressed T-cell IL-17, IFN-γ, and GM-CSF production; MS MSCs increased IL-17 and GM-CSF.
• MS MSCs showed lower IL-10 and higher osteopontin (OPN) production.
• ADAM28 was upregulated in MS MSCs; natalizumab treatment reduced Th17 cells in co-cultures.

Conclusions:

• Blocking ADAM28/OPN interactions or increasing IL-10 may mitigate the pro-inflammatory potential of MS MSCs.
• These strategies could inform clinical applications of MSCs for MS treatment.