Abstract

Objectives

Transfusion of umbilical cord‐derived mesenchymal stem cells (UC‐MSCs) is a novel strategy for treatment of various liver diseases. However, the therapeutic effect of UC‐MSCs is limited because only a few UC‐MSCs migrate towards the damaged regions. In this study, we observed the effects of autophagy on the migration of UC‐MSCs in vitro and in a model of liver ischaemia/reperfusion (I/R) injury.

Materials and Methods

We investigated the effects of autophagy on the status of the cell, release of anti‐inflammatory factors and migration of UC‐MSCs in vitro. The therapeutic effects and in vivo migration of rapamycin‐preconditioned UC‐MSCs were observed in a C57/B6 mouse model of liver I/R injury.

Results

Induction of autophagy by rapamycin enhanced the ability of UC‐MSCs to migrate and release anti‐inflammatory cytokines as well as increased expression of CXCR4 without affecting cell viability. Inhibition of CXCR4 activation markedly decreased migration of these cells. In a mouse model of liver I/R injury, we found significantly upregulated expression of CXCR12 in the damaged liver. More rapamycin‐preconditioned UC‐MSCs migrated towards the ischaemic regions than 3‐methyladenine‐preconditioned or non‐preconditioned UC‐MSCs, leading to improvement in hepatic performance, pathological changes and levels of inflammatory cytokines. These effects were abolished by AMD3100.

Conclusions

Preconditioning of UC‐MSCs by rapamycin afforded increased protection against liver I/R injury by enhancing immunosuppression and strengthening the homing and migratory capacity of these cells via the CXCR4/CXCL12 axis.