PMID- 30311501
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220414
IS  - 1555-3892 (Electronic)
IS  - 0963-6897 (Print)
IS  - 0963-6897 (Linking)
VI  - 27
IP  - 11
DP  - 2018 Nov
TI  - Exosomes Derived from IDO1-Overexpressing Rat Bone Marrow Mesenchymal Stem Cells 
      Promote Immunotolerance of Cardiac Allografts.
PG  - 1657-1683
LID - 10.1177/0963689718805375 [doi]
AB  - BACKGROUND: The immunosuppressive activity of mesenchymal stem cells (MSCs) has 
      been exploited to induce tolerance after organ transplantation. The indoleamine 
      2,3-dioxygenase (IDO) may have beneficial effects in the immunoregulatory 
      properties of MSCs. It was recently revealed that exosomes derived from MSCs play 
      important roles in mediating the biological functions of MSCs. This study aimed 
      to explore the roles of exosomes derived from MSCs in the induction of immune 
      tolerance. METHODS: Dendritic cells (DCs) and T-cells were cultured with exosomes 
      derived from rat bone marrow MSCs (BMSCs) overexpressing IDO1 or controls. For 
      the in-vivo study, rats received heart transplants and were treated with exosomes 
      from IDO-BMSCs and heart function was evaluated. Flow cytometry was used to 
      detect expression of cell surface markers. Cytokine levels were detected in 
      culture supernatants or serum samples. Protein and microRNA expressions in 
      exosomes were investigated by chips. RESULTS: Exosomes from IDO-BMSCs cultured 
      with DCs and T-cells (1) downregulated CD40, CD86, CD80, MHC-II, CD45RA, 
      CD45RA+CD45RB, OX62, and upregulated CD274 expression, (2) increased the number 
      of regulatory T-cells (Tregs) and decreased the number of CD8+ T-cells, and (3) 
      decreased the levels of pro-inflammatory cytokines, but increased the levels of 
      anti-inflammatory cytokines compared with the other groups. Transplanted rats, 
      which were injected with exosomes from IDO-BMSCs, had reduced allograft-targeting 
      immune responses and improved cardiac allograft function. Exosomes secreted by 
      IDO-BMSCs exhibited significant upregulations of the immunoregulatory protein 
      FHL-1, miR-540-3p, and a downregulation of miR-338-5p. CONCLUSION: Exosomes 
      derived from IDO-BMSCs can be used to promote immunotolerance and prolong the 
      survival of cardiac allografts.
FAU - He, Ji-Gang
AU  - He JG
AD  - Department of Cardiovascular Surgery, First People's Hospital of Yunnan Province, 
      Kunming, Yunnan Province, China.
FAU - Xie, Qiao-Li
AU  - Xie QL
AD  - Department of Cardiovascular Surgery, First People's Hospital of Yunnan Province, 
      Kunming, Yunnan Province, China.
FAU - Li, Bei-Bei
AU  - Li BB
AD  - Department of Cardiovascular Surgery, First People's Hospital of Yunnan Province, 
      Kunming, Yunnan Province, China.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Department of Cardiology, First People's Hospital of Yunnan Province, Kunming, 
      Yunnan Province, China.
FAU - Yan, Dan
AU  - Yan D
AD  - Department of Intensive Care Unit, First People's Hospital of Yunnan Province, 
      Yunnan Province, China.
LA  - eng
PT  - Journal Article
DEP - 20181012
PL  - United States
TA  - Cell Transplant
JT  - Cell transplantation
JID - 9208854
SB  - IM
PMC - PMC6299201
OTO - NOTNLM
OT  - 3-dioxygenase
OT  - bone marrow mesenchymal stem cells
OT  - cardiac allograft
OT  - exosomes
OT  - immunotolerance
OT  - indoleamine 2
COIS- Declaration of Conflicting Interests: The authors declared no potential conflicts 
      of interest with respect to the research, authorship, and/or publication of this 
      article.
EDAT- 2018/10/13 06:00
MHDA- 2018/10/13 06:01
PMCR- 2018/11/01
CRDT- 2018/10/13 06:00
PHST- 2018/10/13 06:00 [pubmed]
PHST- 2018/10/13 06:01 [medline]
PHST- 2018/10/13 06:00 [entrez]
PHST- 2018/11/01 00:00 [pmc-release]
AID - 10.1177_0963689718805375 [pii]
AID - 10.1177/0963689718805375 [doi]
PST - ppublish
SO  - Cell Transplant. 2018 Nov;27(11):1657-1683. doi: 10.1177/0963689718805375. Epub 
      2018 Oct 12.