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

Biochem Biophys Res Commun. 2021 Dec 20:584:87-94. doi: 10.1016/j.bbrc.2021.10.078. Epub 2021 Nov 2.

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.

Keywords: CXCL9; Cell therapy; Liver fibrosis; Umbilical cord mesenchymal stem cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • CXCL9 protein, human
  • Chemokine CXCL9