PMID- 36707501
OWN - NLM
STAT- MEDLINE
DCOM- 20230131
LR  - 20230324
IS  - 2041-4889 (Electronic)
VI  - 14
IP  - 1
DP  - 2023 Jan 28
TI  - Interleukin-18-primed human umbilical cord-mesenchymal stem cells achieve 
      superior therapeutic efficacy for severe viral pneumonia via enhancing T-cell 
      immunosuppression.
PG  - 66
LID - 10.1038/s41419-023-05597-3 [doi]
LID - 66
AB  - Coronavirus disease 2019 (COVID-19) treatments are still urgently needed for 
      critically and severely ill patients. Human umbilical cord-mesenchymal stem cells 
      (hUC-MSCs) infusion has therapeutic benefits in COVID-19 patients; however, 
      uncertain therapeutic efficacy has been reported in severe patients. In this 
      study, we selected an appropriate cytokine, IL-18, based on the special cytokine 
      expression profile in severe pneumonia of mice induced by H1N1virus to prime 
      hUC-MSCs in vitro and improve the therapeutic effect of hUC-MSCs in vivo. In 
      vitro, we demonstrated that IL-18-primed hUC-MSCs (IL18-hUCMSC) have higher 
      proliferative ability than non-primed hUC-MSCs (hUCMSCcon). In addition, VCAM-1, 
      MMP-1, TGF-beta1, and some chemokines (CCL2 and CXCL12 cytokines) are more highly 
      expressed in IL18-hUCMSCs. We found that IL18-hUCMSC significantly enhanced the 
      immunosuppressive effect on CD3(+) T-cells. In vivo, we demonstrated that 
      IL18-hUCMSC infusion could reduce the body weight loss caused by a viral 
      infection and significantly improve the survival rate. Of note, IL18-hUCMSC can 
      also significantly attenuate certain clinical symptoms, including reduced 
      activity, ruffled fur, hunched backs, and lung injuries. Pathologically, 
      IL18-hUCMSC transplantation significantly enhanced the inhibition of 
      inflammation, viral load, fibrosis, and cell apoptosis in acute lung injuries. 
      Notably, IL18-hUCMSC treatment has a superior inhibitory effect on T-cell 
      exudation and proinflammatory cytokine secretion in bronchoalveolar lavage fluid 
      (BALF). Altogether, IL-18 is a promising cytokine that can prime hUC-MSCs to 
      improve the efficacy of precision therapy against viral-induced pneumonia, such 
      as COVID-19.
CI  - (c) 2023. The Author(s).
FAU - Liao, Yan
AU  - Liao Y
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Fu, Zeqin
AU  - Fu Z
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Huang, Yinfu
AU  - Huang Y
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Wu, Shiduo
AU  - Wu S
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Wang, Zhen
AU  - Wang Z
AD  - College of Veterinary Medicine, South China Agricultural University, Guangzhou, 
      510642, China.
FAU - Ye, Shaotang
AU  - Ye S
AD  - College of Veterinary Medicine, South China Agricultural University, Guangzhou, 
      510642, China.
FAU - Zeng, Weijie
AU  - Zeng W
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Zeng, Guifang
AU  - Zeng G
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Li, Duanduan
AU  - Li D
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Yang, Yulin
AU  - Yang Y
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Pei, Ke
AU  - Pei K
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Yang, Jian
AU  - Yang J
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Hu, Zhiwei
AU  - Hu Z
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Liang, Xiao
AU  - Liang X
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China.
FAU - Hu, Junyuan
AU  - Hu J
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China. 
      hujunyuan2020@163.com.
FAU - Liu, Muyun
AU  - Liu M
AD  - National-Local Associated Engineering Laboratory for Personalized Cell Therapy, 
      Shenzhen, 518054, China. liumuyun@nlelpct.com.
FAU - Jin, Juan
AU  - Jin J
AD  - Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese 
      Medical University (Zhejiang Provincial Hospital of Traditional Chinese 
      Medicine), Hangzhou, 310000, China. lang_018@163.com.
FAU - Cai, Cheguo
AU  - Cai C
AUID- ORCID: 0000-0002-3712-1696
AD  - Shenzhen Beike Biotechnology Co., Ltd, Shenzhen, 518054, China. 
      cheguo_cai@whu.edu.cn.
AD  - Key Laboratory of Systems Health Science of Zhejiang Province, School of Life 
      Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of 
      Sciences, Hangzhou, 310024, China. cheguo_cai@whu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230128
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Interleukin-18)
RN  - 0 (Cytokines)
SB  - IM
MH  - Humans
MH  - Mice
MH  - Animals
MH  - Interleukin-18/metabolism
MH  - Umbilical Cord/metabolism
MH  - T-Lymphocytes/metabolism
MH  - *COVID-19/metabolism
MH  - Cytokines/metabolism
MH  - *Pneumonia, Viral/therapy/metabolism
MH  - Immunosuppression Therapy
MH  - *Mesenchymal Stem Cells/metabolism
MH  - *Mesenchymal Stem Cell Transplantation
PMC - PMC9883134
COIS- The authors declare no competing interests.
EDAT- 2023/01/28 06:00
MHDA- 2023/02/01 06:00
PMCR- 2023/01/28
CRDT- 2023/01/27 23:23
PHST- 2022/08/30 00:00 [received]
PHST- 2023/01/16 00:00 [accepted]
PHST- 2023/01/12 00:00 [revised]
PHST- 2023/01/28 06:00 [pubmed]
PHST- 2023/02/01 06:00 [medline]
PHST- 2023/01/27 23:23 [entrez]
PHST- 2023/01/28 00:00 [pmc-release]
AID - 10.1038/s41419-023-05597-3 [pii]
AID - 5597 [pii]
AID - 10.1038/s41419-023-05597-3 [doi]
PST - epublish
SO  - Cell Death Dis. 2023 Jan 28;14(1):66. doi: 10.1038/s41419-023-05597-3.