In vitro allogeneic immune cell response to mesenchymal stromal cells derived from human adipose in patients with rheumatoid arthritis.

We investigated the regulatory activity of human adipose-derived mesenchymal stromal cells (MSCs) (n=10) towards immune cells in a cohort of 84 rheumatoid arthritis (RA) patients, 36 apparently healthy controls. We co-cultured MSCs with lymphocyte subsets of T, B, and T regulatory cells (Tregs). Levels of the pro- and anti-inflammatory markers (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10)) were estimated in serum and co-culture supernatants. The study revealed a two-fold increase in the proportion of Tregs and an increased level of CD4CD25FoxP3. MSCs altered T cell, B cell, and Treg cytokine production during an anti-inflammatory immune response. The MSCs inhibited CD3+T cell-mediated TNF-α secretion, upregulated IL-10, and suppressed the production of autoantibodies against citrullinated protein antigens produced by B cells. These data offer insight into the interactions between allogeneic MSCs and immune cells, and elucidate the dose-dependent modulation of MSCs.