Branched chain amino acids improve mesenchymal stem cell proliferation, reducing nuclear factor kappa B expression and modulating some inflammatory properties.

OBJECTIVES

The essential branched chain amino acids (BCAAs) valine, leucine, and isoleucine, are widely studied because of their effects on immunity and metabolism. Mesenchymal stem cells (MSCs) are a type of cell also studied due to their immunomodulatory properties. Since both BCAAs and MSCs have immunomodulatory capacity, the objective of this study was to evaluate the influence of BCAAs on some immunomodulatory aspects of MSCs.

METHODS

MSCs were cultivated in BCAA-supplemented media to evaluate metabolic activity, including cell cycle, proliferative nuclear cell antigen, peroxisome proliferator-activated receptor gamma coactivator 1-alpha, avian myelocytomatosis viral oncogene homolog, peroxisome proliferator activated receptor gamma, nuclear factor kappa B (NFкB), and signal transducers and activators of transcription 3 (STAT-3) expression. Additionally, some inflammatory mediators' synthesis, such as interleukin (IL) 1-beta, IL-10, granulocyte-macrophage colony-stimulating factor, transforming growth factor beta, nitric oxide, and prostaglandin E, were also evaluated.

RESULTS

Supplementation with BCAA led not only to increased MSC proliferation with more cells in the S, G2, and M cycle phases, but also to increased metabolic activity. BCAA supplementation also altered the immunomodulatory capacity of MSCs by decreasing the p-NFкB/NFкB and increasing the p-STAT-3/STAT-3 gene expression ratios, in addition to increasing synthesis of the antiinflammatory mediators transforming growth factor beta and prostaglandin E. Finally, MSCs cultivated in BCAA-supplemented media was shown to decrease the IL-6 and tumor necrosis factor alpha production by macrophages.

CONCLUSIONS

BCAA supplementation affected some immunoregulatory aspects of MSCs.