PMID- 36931619
OWN - NLM
STAT- MEDLINE
DCOM- 20230602
LR  - 20230614
IS  - 1873-2399 (Electronic)
IS  - 0301-472X (Linking)
VI  - 122
DP  - 2023 Jun
TI  - Human umbilical cord mesenchymal stem cells ameliorate acute graft-versus-host 
      disease by elevating phytosphingosine.
PG  - 19-29
LID - S0301-472X(23)00070-X [pii]
LID - 10.1016/j.exphem.2023.03.002 [doi]
AB  - Acute graft-versus-host disease (aGVHD) is a prominent barrier to allogeneic 
      hematopoietic stem cell transplantation (allo-HSCT) and even leads to death after 
      HSCT. Human umbilical cord mesenchymal stem cells (HUCMSCs) are effective in 
      aGVHD treatment and have mild side effects, but the underlying mechanisms remain 
      unclear. Phytosphingosine (PHS) is known to prevent the loss of moisture from the 
      skin; regulate epidermal cell growth, differentiation, and apoptosis; and exert 
      bactericidal and anti-inflammatory effects. In this study, our results revealed 
      the efficacy of HUCMSCs in alleviating aGVHD in a murine model, with striking 
      changes in metabolism and significantly elevated PHS levels due to sphingolipid 
      metabolism. In vitro, PHS reduced CD4(+) T-cell proliferation, enhanced 
      apoptosis, and reduced T helper 1 (Th1) cell differentiation. Transcriptional 
      analysis of donor CD4(+) T cells treated with PHS revealed significant decreases 
      in transcripts regulating proinflammatory pathways, such as nuclear factor 
      (NF)-kappaB. In vivo, the administration of PHS significantly ameliorated aGVHD 
      development. Collectively, these beneficial effects indicate proof of concept 
      that sphingolipid metabolites could be a safe and effective means to prevent 
      aGVHD in the clinic.
CI  - Copyright (c) 2023. Published by Elsevier Inc.
FAU - Hong, Tao
AU  - Hong T
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China.
FAU - Wang, Rui
AU  - Wang R
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China; Jinfeng 
      Laboratory, Chongqing, China.
FAU - Yang, Guancui
AU  - Yang G
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China; Department 
      of Hematology, Affiliated Hospital of North Sichuan Medical College, Nanchong, 
      China.
FAU - Wang, Xiaoqi
AU  - Wang X
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China.
FAU - Zeng, Lingyu
AU  - Zeng L
AD  - Department of Hematology, The Affiliated Hospital of Xuzhou Medical University, 
      Xuzhou, Jiangsu, China.
FAU - Yang, Shijie
AU  - Yang S
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China; Jinfeng 
      Laboratory, Chongqing, China.
FAU - Wei, Jin
AU  - Wei J
AD  - Department of Hematology, Affiliated Hospital of North Sichuan Medical College, 
      Nanchong, China.
FAU - Gao, Qiangguo
AU  - Gao Q
AD  - Department of Cell Biology, College of Basic Medicine, Army Medical University, 
      Chongqing, China. Electronic address: qiangguogao@163.com.
FAU - Zhang, Xi
AU  - Zhang X
AD  - Medical Center of Hematology, Xinqiao Hospital, State Key Laboratory of Trauma, 
      Burns and Combined Injury, Army Medical University, Chongqing, China; Jinfeng 
      Laboratory, Chongqing, China. Electronic address: zhangxxi@sina.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230316
PL  - Netherlands
TA  - Exp Hematol
JT  - Experimental hematology
JID - 0402313
RN  - GIN46U9Q2Q (phytosphingosine)
RN  - 0 (Sphingolipids)
SB  - IM
MH  - Humans
MH  - Animals
MH  - Mice
MH  - *Hematopoietic Stem Cell Transplantation/methods
MH  - *Graft vs Host Disease/prevention & control/etiology
MH  - *Mesenchymal Stem Cells
MH  - Sphingolipids
MH  - Umbilical Cord
MH  - Acute Disease
EDAT- 2023/03/18 06:00
MHDA- 2023/06/02 06:42
CRDT- 2023/03/17 20:35
PHST- 2022/11/12 00:00 [received]
PHST- 2023/02/28 00:00 [revised]
PHST- 2023/03/08 00:00 [accepted]
PHST- 2023/06/02 06:42 [medline]
PHST- 2023/03/18 06:00 [pubmed]
PHST- 2023/03/17 20:35 [entrez]
AID - S0301-472X(23)00070-X [pii]
AID - 10.1016/j.exphem.2023.03.002 [doi]
PST - ppublish
SO  - Exp Hematol. 2023 Jun;122:19-29. doi: 10.1016/j.exphem.2023.03.002. Epub 2023 Mar 
      16.