Therapeutic effects of CXCL9-overexpressing human umbilical cord mesenchymal stem cells on liver fibrosis in rats.

Abstract

Umbilical cord mesenchymal stem cells (UC-MSCs) transplantation has become a promising treatment for liver fibrosis. However, UC-MSCs have limited anti-fibrosis ability, and their homing ability of UC-MSCs to the injured liver seems to be poor. In our study, we aimed to determine if the CXCL9-overexpressing UC-MSCs could have synergistic anti-fibrosis effects and whether it can promote the homing ability of UC-MSCs. Overexpression of CXCL9 in UC-MSCs (CXCL9-UC-MSCs) was attained by transfecting the lenti-CXCL9-mCherry to naive UC-MSCs. The therapeutic effect of transducted CXCL9-UC-MSCs on both repairing of hepatic fibrosis and target homing were evaluated by comparing with the control of UC-MSCs transfected with empty lenti-mCherry vector. The results revealed that the liver function of CXCL9-UC-MSCs treated group was significantly improved when compared with that of control UC-MSCs (P < 0.05), and the histopathology indicated an obvious decrease of the collagen fiber content and significant disappearing of pseudo-lobules with basically normal morphology of hepatic lobules. Furthermore, liver frozen sections confirmed that CXCL9-UC-MSCs have significantly stronger chemotaxis and stable persistence in the injured liver tissues. In summary, overexpression of CXCL9 could improve the efficacy of UC-MSCs therapy for liver fibrosis repairing on account of an enhanced ability of UC-MSCs in homing to and staying in the injured sites of liver fibrosis in rat models.

• Authors: Yang Li, Jiantao Dong, Ye Zhou, Xueshuai Ye, Ziqi Cai, Xueqian Zhang, Li Shen, Mengya Zhang, Wanxing Zhang, Jianhui Cai
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 584 Pg. 87-94 (12 20 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 34775285 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• CXCL9 protein, human
• Chemokine CXCL9

Topics

• Animals
• Cell Differentiation (genetics)
• Cells, Cultured
• Chemokine CXCL9 (genetics, metabolism)
• Disease Models, Animal
• Hepatocytes (cytology, metabolism)
• Humans
• Liver Cirrhosis (therapy)
• Male
• Mesenchymal Stem Cell Transplantation (methods)
• Mesenchymal Stem Cells (metabolism)
• Rats, Sprague-Dawley
• Transfection
• Transplantation, Heterologous
• Treatment Outcome
• Umbilical Cord (cytology)