Mesenchymal Stem Cells and Their Derived Exosomes Mitigated Hepatic Cirrhosis in Rats by Altering the Expression of miR-23b and miR-221.

BACKGROUND

The therapeutic effect of mesenchymal stem cells (MSCs) in liver cirrhosis is limited by their entrapment in the pulmonary vessels. Thus, the use of MSC-derived exosomes has become a promising strategy. The current work aimed to compare the role of human umbilical cord blood-MSCs (hUCB-MSCs) and their derived exosomes in the alleviation of liver cirrhosis focusing on the role of miR-23b and miR-221 and their direct effectors in inflammatory and autophagic pathways.

METHODS

Rats were divided into six groups normal controls (negative control), liver cirrhosis group (positive control), liver cirrhotic rats that received conditioned media, liver cirrhotic rats that received hUCB-MSCs, cirrhotic rats that received exosomes, and cirrhotic rats that received both hUCB-MSCs and exosomes. The messenger RNA expression of and and were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemical staining for Beclin, P62, and LC3 was performed.

RESULTS

The treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly downregulated (P<0.001, for each), and P62 (P=0.032, P<0.001, P<0.001, respectively). Additionally, the treatment of cirrhotic rats with hUCB-MSCs, exosomes, or the combination of them significantly upregulated , , , and (P<0.001, for each) and (P=0.021, P<0.001, P<0.001, respectively).

CONCLUSION

hUCB-MSCs and their derived exosomes ameliorated liver cirrhosis by anti-inflammatory and anti-fibrotic effects besides modulation of autophagy. The exosomes had a better improvement effect either alone or combined with hUCB-MSCs, as proved by improvement in liver function tests, and molecular, histopathological, and immunohistochemical profiles.