Preconditioning of umbilical cord-derived mesenchymal stem cells by rapamycin increases cell migration and ameliorates liver ischaemia/reperfusion injury in mice via the CXCR4/CXCL12 axis.
Animals
Cell Movement
/ drug effects
Cells, Cultured
Chemokine CXCL12
/ immunology
Humans
Immunosuppressive Agents
/ pharmacology
Ischemic Preconditioning
/ methods
Liver
/ blood supply
Liver Diseases
/ immunology
Mesenchymal Stem Cell Transplantation
/ methods
Mesenchymal Stem Cells
/ drug effects
Mice
Mice, Inbred C57BL
Receptors, CXCR4
/ immunology
Reperfusion Injury
/ immunology
Signal Transduction
/ drug effects
Sirolimus
/ pharmacology
Umbilical Cord
/ cytology
CXCR4
autophagy
liver ischaemia/reperfusion injury
migration
preconditioning
umbilical cord-derived mesenchymal stem cells
Journal
Cell proliferation
ISSN: 1365-2184
Titre abrégé: Cell Prolif
Pays: England
ID NLM: 9105195
Informations de publication
Date de publication:
Mar 2019
Mar 2019
Historique:
received:
16
02
2018
revised:
11
08
2018
accepted:
13
08
2018
pubmed:
12
12
2018
medline:
16
4
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
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. 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. 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. 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.
Identifiants
pubmed: 30537044
doi: 10.1111/cpr.12546
pmc: PMC6496237
doi:
Substances chimiques
Chemokine CXCL12
0
Immunosuppressive Agents
0
Receptors, CXCR4
0
Sirolimus
W36ZG6FT64
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12546Subventions
Organisme : National Natural Science Foundation of China
ID : 81570593
Organisme : National Natural Science Foundation of China
ID : 81770648
Organisme : Sci-tech Research Development Program of Guangzhou City
ID : 158100076
Organisme : Natural Science Foundation of Guangdong Province
ID : 2015A030312013
Organisme : Sun Yat-Sen University Clinical Research 5010 Program
ID : 2014006
Organisme : Sci-tech Research Development Program of Guangdong Province
ID : 2017A020215023
Organisme : Young Teacher Development Program of Sun Yat-sen University
ID : 17ykpy57
Organisme : National Key Research and Development Program
ID : 2017YFA0104304
Informations de copyright
© 2018 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.
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