Effect and mechanisms of combination therapy with adipose-derived mesenchymal stem cells (AD-MSCs) and melatonin in cyclophosphamide (CYP)-induced acute interstitial cystitis (AIC). (A) The AIC group showed the highest urine turbidity and hematuria compared to the other groups. In contrast, the group treated with the combination of AD-MSCs and melatonin showed markedly lower urine turbidity than the groups treated with AD-MSCs or melatonin alone. This test was carried out for 72 h after AIC induction. (B) The urine amount was recorded on the last day of the 72-h period after AIC induction. (C) Number of red blood cells (RBCs) per mL of urine. (D) The mechanisms underlying the effects of the combination of AD-MSCs and melatonin in CYP-induced AIC therapy. These figures were reproduced from articles by Chen et al. 2014 [163] with permission from John Wiley and Sons. TGF-β1, transforming growth factor-beta 1. EB, embryoid bodies. HEMA, hydroxyethyl methacrylate. HO, heme oxygenase. iNOS, inducible nitric oxide synthase. NOX, NADPH oxidase. NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells. NQO, NAD(P)H quinone oxidoreductase. MMP-9, matrix metalloproteinases-9. IL, interleukin. AIC, acute interstitial cystitis. TNF-α, tumor necrosis factor-α. MIF, macrophage migration inhibitory factor. SP, substance P. RBCs, red blood cells. Down arrow, downregulation. Up arrow, upregulation.