Melatonin pretreatment can improve the therapeutic effect of adipose-derived stem cells on CCl₄-induced liver fibrosis

Abstract

In this study, the therapeutic effect of Mel-incubated Adipose-derived mesenchymal stem cells (ADSCs) on CCl₄-induced hepatic fibrosis was investigated. Mice with hepatic fibrosis were intraperitoneally injected with 8% CCl₄ twice a week for 4 weeks. Starting from week 5, mice in the ADSC group and ADSC + Mel group were injected with 1 mL PBS cell suspension containing 1 × 10⁶ ADSCs or ADSCs pretreated with 50 nM Mel twice a week for 2 consecutive weeks. Results: In the model group, severe histopathological changes were observed in the liver, including severe vacuolation, nuclear fragmentation, and liver fibrosis, and these changes were ameliorated by Mel-pretreated ADSCs. RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of proapoptotic genes (Caspase-8, Bax, and Caspase-3) and promoted the expression of an anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9-, TGF-β-, and MMP-2-positive cells were present in the liver tissues of the model group, while the number of positive cells was reduced by Mel-induced ADSCs. ELISA results showed that the ADSC pretreated with Mel also significantly reduced the expression levels of TNF-α and IL-6. Conclusion: ADSCs pretreated with Mel significantly improved CCl₄-induced liver fibrosis.

Keywords:

• Melatonin (Mel)
• Adipose-derived mesenchymal stem cells (ADSCs)
• CCl₄
• liver
• fibrosis

Acknowledgements

Not Applicable.

Ethics approval and Consent to participate

All animal care and experimental protocols were conducted according to the University Policies on the Use and Care of Animals and were approved by the Institutional Animal Experiment Committee of Henan University of Science and Technology, China (Animal License Number: ZHXK20190020).

Author contributions

HJ Wang, YX Yang, RQ Dong, YL Xu, MY Zhang performed the experiments. QX Lv and XG Chen analyzed the data. YY Sun and HJ Wang prepared the manuscript. YM Liu and YY Sun revised the manuscript. ZQ Zhang and YM Liu proposed the concept of the study and directed the design and implementation of the study.

Disclosure statements

The authors declare that they have no competing interests or declarations.

Consent to publish

Not applicable.

Data availability statement

The data underlying this article will be shared by the corresponding author upon reasonable request.

Additional information

Funding

The authors acknowledge the financial support of the National Natural Science Foundation of China (Grant No. U1504325) and the Foundation of Henan Province (Grant No. 31101779).