Paradoxical effects of human adipose tissue-derived mesenchymal stem cells on progression of experimental arthritis in SKG mice.

We evaluated the therapeutic effect of human adipose tissue-derived mesenchymal stem cells (hAd-MSCs) in a SKG arthritis model, a relevant animal model for human rheumatoid arthritis. hAd-MSCs were administered intraperitoneally into the mice for five consecutive days from on day 12 or 34 after arthritis induction, when the average clinical score was 0.5 or 5, respectively. They remarkably suppressed arthritis when administered on day 12. Disease suppression was correlated with reduction of pro-inflammatory cytokines and with increased levels of TGF-β and IL-10 from splenocytes. However, when hAd-MSCs were administered on day 34, the clinical scores were not improved, the histopathological scores were aggravated, and cytokine profiles were differed. Thus, hAd-MSCs showed paradoxical effects, according to the disease phase when they were administered. These suggest that the same cells acted differently depending on the disease progress, and cautions should be paid for safe and effective use of MSCs.