Pretreatment of ADSCs with resveratrol-functionalized selenium nanoparticles alleviate CCl4-induced liver fibrosis in mice.

BACKGROUND

Liver fibrosis (LF) is an abnormal repair reaction after chronic liver injury. Currently, adipose-derived mesenchymal stem cells (ADSCs) are widely used in the treatment of liver diseases. However, the therapeutic effect of ADSCs is affected by the damaged microenvironment. In this study, a resveratrol-functionalized nano‑selenium (Res@SeNPs) formulation was prepared to investigate whether Res@SeNPs pretreatment can enhance the therapeutic effect and alter the potential mechanism of ADSCs in carbon tetrachloride (CCl4) -induced LF in mice.

METHODS

Res@SeNPs were prepared and ADSCs pretreated with Res@SeNPs were cocultured with CCl4-injured BRL-3A cells in vitro. In vivo, ADSCs pretreated with Res@SeNPs were injected into the tail vein of a CCl4-induced LF mouse model.

RESULTS

Res@SeNPs were successfully prepared. In vitro, after coculture with BRL-3A cells, the function of damaged BRL-3A cells was improved. In vivo, Res@SeNPs-pretreated ADSCs effectively alleviated liver function damage and fibrosis in mice with LF. This may be related to the inhibition of oxidative stress, the reduction in apoptosis and the inhibition of the activation of the apoptosis signal-regulated kinase 1/c-Jun N-terminal kinase/p38 mitogen-activated protein kinase (ASK1/JNK/p38) pathway.

CONCLUSION

Our study suggested that Res@SeNPs pretreatment can enhance the therapeutic effect of ADSCs on LF in mice, and in vivo findings indicated the potential mechanism of ADSCs, providing new ideas for the treatment of LF.