PMID- 31891674
OWN - NLM
STAT- MEDLINE
DCOM- 20200724
LR  - 20211125
IS  - 1096-0007 (Electronic)
IS  - 0014-4835 (Print)
IS  - 0014-4835 (Linking)
VI  - 191
DP  - 2020 Feb
TI  - Human umbilical cord mesenchymal stem cells alleviate ongoing autoimmune 
      dacryoadenitis in rabbits via polarizing macrophages into an anti-inflammatory 
      phenotype.
PG  - 107905
LID - S0014-4835(19)30821-8 [pii]
LID - 10.1016/j.exer.2019.107905 [doi]
AB  - Mesenchymal stem cells (MSCs) exhibit beneficial effects on autoimmune 
      dacryoadenitis. However, the underlying mechanisms are not fully understood. In 
      this study, we investigated the therapeutic effect of human umbilical cord 
      mesenchymal stem cells (hUC-MSCs) on rabbit autoimmune dacryoadenitis, an animal 
      model of Sjogren's syndrome (SS) dry eye, and explored whether the effects of 
      MSCs were related to their modulation on macrophage polarization. We have showed 
      that systemic infusion of hUC-MSCs after disease onset efficiently diminished the 
      chronic inflammation in diseased LGs and improved the clinical symptoms. Further 
      analysis revealed that hUC-MSC treatment significantly inhibited the expression 
      of pro-inflammatory M1 macrophage markers iNOS, TNF-alpha and IL-6, and promoted the 
      expression of anti-inflammatory M2 macrophage markers Arg1, CD206, IL-10, IL-4 
      and TGF-beta in LGs. Mechanistically, hUC-MSCs activated AKT pathway in macrophages, 
      resulting in upregulation of M2-associated molecule Arg1, which was partly 
      abolished by PI3K inhibitor, LY294002. Together, our data indicated that hUC-MSCs 
      can skew macrophages into an M2 phenotype via affecting AKT pathway. These data 
      may provide a new insight into the mechanisms of hUC-MSCs in the therapy of SS 
      dry eye.
CI  - Copyright (c) 2020 Elsevier Ltd. All rights reserved.
FAU - Lu, Xiaoxiao
AU  - Lu X
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Li, Na
AU  - Li N
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Zhao, Lu
AU  - Zhao L
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Guo, Di
AU  - Guo D
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Yi, Huanfa
AU  - Yi H
AD  - Central Laboratory of the Eastern Division, The First Hospital, Jilin University, 
      Changchun, China.
FAU - Yang, Liyuan
AU  - Yang L
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Liu, Xun
AU  - Liu X
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China.
FAU - Sun, Deming
AU  - Sun D
AD  - Doheny Eye Institute, And Department of Ophthalmology, David Geffen School of 
      Medicine, University of California Los Angeles (UCLA), Los Angeles, USA.
FAU - Nian, Hong
AU  - Nian H
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China. 
      Electronic address: nianhong@126.com.
FAU - Wei, Ruihua
AU  - Wei R
AD  - Tianjin Key Laboratory of Retinal Functions and Diseases, Eye Institute and 
      School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, China. 
      Electronic address: rwei@tmu.edu.cn.
LA  - eng
GR  - R01 EY018827/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191228
PL  - England
TA  - Exp Eye Res
JT  - Experimental eye research
JID - 0370707
RN  - 0 (Anti-Inflammatory Agents)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*metabolism
MH  - Autoimmune Diseases/immunology/*prevention & control
MH  - Blotting, Western
MH  - Cell Culture Techniques
MH  - Dacryocystitis/immunology/*prevention & control
MH  - Disease Models, Animal
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Macrophage Activation
MH  - Macrophages/*immunology
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*physiology
MH  - Phenotype
MH  - Rabbits
MH  - Real-Time Polymerase Chain Reaction
MH  - Umbilical Cord/*cytology
PMC - PMC8612174
MID - NIHMS1755898
OTO - NOTNLM
OT  - Autoimmune dacryoadenitis
OT  - Human umbilical cord mesenchymal stem cells
OT  - Inflammatory mediators
OT  - Macrophages
COIS- Conflicting interest statement The authors declare that they have no competing 
      financial interests.
EDAT- 2020/01/01 06:00
MHDA- 2020/07/25 06:00
PMCR- 2021/11/24
CRDT- 2020/01/01 06:00
PHST- 2019/11/05 00:00 [received]
PHST- 2019/12/08 00:00 [revised]
PHST- 2019/12/27 00:00 [accepted]
PHST- 2020/01/01 06:00 [pubmed]
PHST- 2020/07/25 06:00 [medline]
PHST- 2020/01/01 06:00 [entrez]
PHST- 2021/11/24 00:00 [pmc-release]
AID - S0014-4835(19)30821-8 [pii]
AID - 10.1016/j.exer.2019.107905 [doi]
PST - ppublish
SO  - Exp Eye Res. 2020 Feb;191:107905. doi: 10.1016/j.exer.2019.107905. Epub 2019 Dec 
      28.