PMID- 31892638
OWN - NLM
STAT- MEDLINE
DCOM- 20210713
LR  - 20210713
IS  - 1708-8267 (Electronic)
IS  - 1081-5589 (Linking)
VI  - 68
IP  - 3
DP  - 2020 Mar
TI  - Indoleamine 2,3-dioxgenase-transfected mesenchymal stem cells suppress heart 
      allograft rejection by increasing the production and activity of dendritic cells 
      and regulatory T cells.
PG  - 728-737
LID - 10.1136/jim-2019-001160 [doi]
AB  - Expression of indoleamine 2,3-dioxygenase (IDO) in mesenchymal stem cells (MSC) 
      is thought to contribute to MSC-mediated immunosuppression. A lentiviral-based 
      transgenic system was used to generate bone marrow stem cells (BMSC) which stably 
      expressed IDO (IDO-BMSCs). Coculture of IDO-BMSCs with dendritic cells (DC) or T 
      cells was used to evaluate the immunomodulatory effect of IDO-BMSCs. A 
      heterotopic heart transplant model in rats was used to evaluate allograft 
      rejection after IDO-BMSC treatment. Mechanisms of IDO-BMSC-mediated 
      immunosuppression were investigated by evaluating levels of proinflammatory and 
      anti-inflammatory cytokines, and production of Tregs. A significant decrease in 
      DC marker-positive cells and a significant increase in Tregs were observed in 
      IDO-BMSC cocultured. Treatment of transplanted rats with IDO-BMSCs was associated 
      with significantly prolonged graft survival. Compared with the control groups, 
      transplanted animals treated with IDO-BMSCs had a (1) significantly higher 
      ejection fraction and fractional shortening, (2) significantly lower expression 
      of CD86, CD80, and MHCII, and significantly higher expression in CD274, and 
      Tregs, and (3) significantly higher levels of interleukin-10 (IL-10), 
      transforming growth factor beta-1 (TGF-beta1), TGF-beta2, and TGF-beta3, and significantly 
      lower levels of IL-2 and interferon gamma. Our results expand our understanding 
      of the molecular mechanisms underlying suppression of heart allograft rejection 
      via IDO-expressing BMSCs.
CI  - (c) American Federation for Medical Research 2020. No commercial re-use. See rights 
      and permissions. Published by BMJ.
FAU - He, Ji-Gang
AU  - He JG
AD  - Department of Cardiac and Vascular Surgery, First People's Hospital of Yunnan 
      Province, Kunming, China.
FAU - Li, Bei-Bei
AU  - Li BB
AD  - Department of Cardiac and Vascular Surgery, First People's Hospital of Yunnan 
      Province, Kunming, China.
FAU - Zhou, Liang
AU  - Zhou L
AD  - Department of Cardiology, First People's Hospital of Yunnan Province, Kunming, 
      China.
FAU - Yan, Dan
AU  - Yan D
AD  - Intensive Care Unit, First People's Hospital of Yunnan Province, Kunming, China.
FAU - Xie, Qiao-Li
AU  - Xie QL
AD  - Department of Cardiac and Vascular Surgery, First People's Hospital of Yunnan 
      Province, Kunming, China.
FAU - Zhao, Wei
AU  - Zhao W
AUID- ORCID: 0000-0003-0187-9224
AD  - Department of Cardiac and Vascular Surgery, First People's Hospital of Yunnan 
      Province, Kunming, China jiganghe999@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191231
PL  - England
TA  - J Investig Med
JT  - Journal of investigative medicine : the official publication of the American 
      Federation for Clinical Research
JID - 9501229
RN  - 0 (Cytokines)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 130068-27-8 (Interleukin-10)
SB  - IM
MH  - Allografts
MH  - Animals
MH  - Bone Marrow Cells
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/metabolism
MH  - Dendritic Cells/metabolism
MH  - Graft Rejection/*prevention & control
MH  - *Heart Transplantation
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/immunology/*metabolism
MH  - Interleukin-10/metabolism
MH  - Lentivirus/genetics
MH  - Male
MH  - Mesenchymal Stem Cells/drug effects/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Rats, Wistar
MH  - Stem Cells/metabolism
MH  - T-Lymphocytes, Regulatory/metabolism
MH  - Transfection
MH  - Transplantation Tolerance
OTO - NOTNLM
OT  - stem cells
COIS- Competing interests: None declared.
EDAT- 2020/01/02 06:00
MHDA- 2021/07/14 06:00
CRDT- 2020/01/02 06:00
PHST- 2019/12/07 00:00 [accepted]
PHST- 2020/01/02 06:00 [pubmed]
PHST- 2021/07/14 06:00 [medline]
PHST- 2020/01/02 06:00 [entrez]
AID - jim-2019-001160 [pii]
AID - 10.1136/jim-2019-001160 [doi]
PST - ppublish
SO  - J Investig Med. 2020 Mar;68(3):728-737. doi: 10.1136/jim-2019-001160. Epub 2019 
      Dec 31.