PMID- 32184939
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200928
IS  - 1948-0210 (Print)
IS  - 1948-0210 (Electronic)
IS  - 1948-0210 (Linking)
VI  - 12
IP  - 2
DP  - 2020 Feb 26
TI  - C-C chemokine receptor type 2-overexpressing exosomes alleviated experimental 
      post-stroke cognitive impairment by enhancing microglia/macrophage M2 
      polarization.
PG  - 152-167
LID - 10.4252/wjsc.v12.i2.152 [doi]
AB  - BACKGROUND: Human-derived mesenchymal stromal cells have been shown to improve 
      cognitive function following experimental stroke. The activity of exosomes has 
      been verified to be comparable to the therapeutic effects of mesenchymal stromal 
      cells. However, the effects of exosomes derived from human umbilical cord 
      mesenchymal stem cells (HUC-MSCs) (Exo(Ctrl)) on post-stroke cognitive impairment 
      (PSCI) have rarely been reported. Moreover, whether exosomes derived from C-C 
      chemokine receptor type 2 (CCR2)-overexpressing HUC-MSCs (Exo(CCR2)) can enhance 
      the therapeutic effects on PSCI and the possible underlying mechanisms have not 
      been studied. AIM: To investigate the effects of Exo(Ctrl) on PSCI and whether 
      Exo(CCR2) can enhance therapeutic effects on PSCI. METHODS: Transmission electron 
      microscopy, qNano((R)) particles analyzer, and Western blotting were employed to 
      determine the morphology and CCR2 expression of Exo(Ctrl) or Exo(CCR2). ELISA was 
      used to study the binding capacity of exosomes to CC chemokine ligand 2 (CCL2) in 
      vivo. After the intravenous injection of Exo(Ctrl) or Exo(CCR2) into experimental 
      rats, the effect of Exo(Ctrl) and Exo(CCR2) on PSCI was assessed by Morris water 
      maze. Remyelination and oligodendrogenesis were analyzed by Western blotting and 
      immunofluorescence microscopy. QRT-PCR and immunofluorescence microscopy were 
      conducted to compare the microglia/macrophage polarization. The infiltration and 
      activation of hematogenous macrophages were analyzed by Western blotting and 
      transwell migration analysis. RESULTS: CCR2-overexpressing HUC-MSCs loaded the 
      CCR2 receptor into their exosomes. The morphology and diameter distribution 
      between Exo(Ctrl) and Exo(CCR2) showed no significant difference. Exo(CCR2) bound 
      significantly to CCL2 but Exo(Ctrl) showed little CCL2 binding. Although both 
      Exo(CCR2) and Exo(Ctrl) showed beneficial effects on PSCI, oligodendrogenesis, 
      remyelination, and microglia/macrophage polarization, Exo(CCR2) exhibited a 
      significantly superior beneficial effect. We also found that Exo(CCR2) could 
      suppress the CCL2-induced macrophage migration and activation in vivo and in 
      vitro, compared with Exo(Ctrl) treated group. CONCLUSION: CCR2 over-expression 
      enhanced the therapeutic effects of exosomes on the experimental PSCI by 
      promoting M2 microglia/macrophage polarization, enhancing oligodendrogenesis and 
      remyelination. These therapeutic effects are likely through suppressing the 
      CCL2-induced hematogenous macrophage migration and activation.
CI  - (c)The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights 
      reserved.
FAU - Yang, Huai-Chun
AU  - Yang HC
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Andrology, the First Affiliated Hospital, Sun Yat-sen University, 
      Guangzhou 510000, Guangdong Province, China.
FAU - Wu, Rui
AU  - Wu R
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Zheng, Hai-Qing
AU  - Zheng HQ
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Zhang, Li-Ying
AU  - Zhang LY
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Luo, Jing
AU  - Luo J
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Li, Li-Li
AU  - Li LL
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China.
FAU - Hu, Xi-Quan
AU  - Hu XQ
AD  - Department of Rehabilitation Medicine, the Third Affiliated Hospital, Sun Yat-sen 
      University, Guangzhou 510000, Guangdong Province, China. sysu_hu@163.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - World J Stem Cells
JT  - World journal of stem cells
JID - 101535826
PMC - PMC7062036
OTO - NOTNLM
OT  - C-C chemokine receptor type 2
OT  - Cognitive impairment
OT  - Exosomes
OT  - Microglia/macrophage polarization
OT  - Remyelination
OT  - Stroke
COIS- Conflict-of-interest statement: The authors declare no conflicts of interest.
EDAT- 2020/03/19 06:00
MHDA- 2020/03/19 06:01
PMCR- 2020/02/26
CRDT- 2020/03/19 06:00
PHST- 2019/10/22 00:00 [received]
PHST- 2019/12/27 00:00 [revised]
PHST- 2020/01/19 00:00 [accepted]
PHST- 2020/03/19 06:00 [entrez]
PHST- 2020/03/19 06:00 [pubmed]
PHST- 2020/03/19 06:01 [medline]
PHST- 2020/02/26 00:00 [pmc-release]
AID - 10.4252/wjsc.v12.i2.152 [doi]
PST - ppublish
SO  - World J Stem Cells. 2020 Feb 26;12(2):152-167. doi: 10.4252/wjsc.v12.i2.152.