Priming of rat bone marrow-derived mesenchymal stem cells with curcumin induces an anti-inflammatory M2 phenotype in J774A.1 macrophage cell line.

CONTEXT: In recent years, several strategies have been used to enhance mesenchymal stem cells’ (MSCs) immunomodulatory and therapeutic potential. Curcumin (Cur), the main active component of turmeric from the Curcuma longa plant, might improve the effectiveness of MSCs. MATERIALS AND

METHODS

Lipopolysaccharide (LPS)-stimulated J774.1 macrophages were treated with either Cur (10, 20, and 40 µM) or Rat bone marrow-derived MSCs-conditioned media (MSCs-CM) cultured in the presence or absence of Cur. Macrophage polarization was evaluated by qRT-PCR for M1/M2 markers, while ELISA and the Griess assay quantified TNF-α/TGF-β and NO levels, respectively.

RESULTS

Treatment with Cur-primed MSCs-CM potently induced an anti-inflammatory M2 phenotype in LPS-stimulated macrophages. It demonstrated superior efficacy over free Cur by significantly upregulating TGF-β at 40 µM and producing a broader, more consistent suppression of key M1 markers, including IL-1β, IL-12, and TNF-α. While 10 µM Cur was the strongest inducer of IL-10 and Cur alone was more potent at suppressing IL-6 and nitric oxide production, the primed MSCs-CM provided a more balanced and robust immunomodulatory profile, effectively countering the pro-inflammatory effects of low-dose Cur.

CONCLUSIONS

In conclusion, priming MSCs with Cur generates a synergistic therapy that capitalizes on the strengths of both components. This strategy yields a potent, multifaceted anti-inflammatory agent capable of effectively reprogramming macrophages toward a therapeutic M2 phenotype, presenting a promising cell-free approach for treating inflammatory diseases.