Anti-Arthritogenic Property of Interleukin 10-Expressing Human Amniotic MSCs Generated by Gene Editing in...

Although stem cells are promising tools for the treatment of arthritis, their therapeutic effects remain controversial. In this study, we investigated the therapeutic properties of interleukin (IL)-10-overexpressing human amniotic mesenchymal stem cells (AMMs) generated via gene editing in a collagen-induced mouse model. IL-10 was inserted into the genomic loci of AMMs via transcription activator-like effector nucleases. In vitro immunomodulatory effects of IL-10-overexpressing AMMs (AMM/I) were evaluated and their anti-arthritogenic properties were determined in collagen-induced arthritis (CIA) mice. Transplantation of AMM/I attenuates CIA progression. In addition, the regulatory T cell population was increased, while T helper-17 cell activation was suppressed by AMM/I administration in CIA mice. Consistently, AMM/I injection increased proteoglycan expression, while reducing inflammation and the expression levels of the pro-inflammatory factors, IL-1 β, IL-6, monocyte chemoattractant protein-1, and tumor necrosis factor- α, in joint tissues. In conclusion, use of IL-10-edited human AMM/I may be a novel therapeutic strategy for the treatment of arthritis.