Dimethyl fumarate as an immunomodulatory enhancer of adipose-derived mesenchymal stem cells: therapeutic implications

Abstract

Adipose-drive stem cells (ASCs) are similar to Mesenchymal stem cells (MSCs), which are considered as multipotent progenitors that have capable of immunomodulation, self-renewal and differentiation into multiple cell lineages that can be used in cancer therapy or immune diseases. Dimethyl fumarate (DMF) is one of the important drugs with modulating function for treatment of various immune disease. The primary aim of this study was to investigate how dimethyl fumarate influences the immunomodulatory profile and functional properties of adipose‑derived mesenchymal stem cells under inflammatory conditions. Adipose-stimulating stem cells (ASCs) were isolated from the abdominal adipose tissue of ten patients via liposuction, and DMF was added after inducing inflammatory conditions with inflammatory cytokines such as IFN-γ and TNF-α. Cell culture and RT-PCR were performed to measure the expression of immunomodulatory factors such as Galectin-1/3, HGF, HO-1, CXCL-8, and IL-6. Flow cytometry for mesenchymal stem cell nature and confirmation was done. Fat and bone staining was performed to test the functional differentiation of these cells. ASCs treated with DMF at 0.01-100 μM concentration at 2 days showed the enhancement of CXCL-8 and IL-6 gene expression notably, whereas, HGF, and Galectin-1 reduced. Moreover, Galectin-3 and HO-1 depicted no significant difference compared to the control group. Further, Alizarin Red and Oil Red staining verified the change of MSCs toward adipose and osteogenic differentiation. ASCs are positive for markers including CD73+, CD90+, and CD105+ antigens by abs staining conjugated to fluorescence dye. Our study confirmed that ASCs combined with DMF have increasingly important roles through immune-modulatory properties by secreting mediators, which can suppress, improve, alter, or change the microenvironment of disease. Despite ongoing progress, the underlying stimulatory and regulatory mechanisms remain incompletely understood. The gap between pre‑clinical findings and clinical applications highlights the need for further investigation. Extensive research is still required to elucidate how therapeutic interventions achieve efficacy, ensure safety, and identify optimal strategies for targeting different organs in combination with other pharmacological agents.

Keywords: Adipose-derived mesenchymal stem cells; Dimethyl fumarate; Galectin-1; Hepatocyte growth factor; Immunomodulatory.