PMID- 33571747
OWN - NLM
STAT- MEDLINE
DCOM- 20210622
LR  - 20210622
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 94
DP  - 2021 May
TI  - Mesenchymal stem cell carriers enhance antitumor efficacy induced by oncolytic 
      reovirus in acute myeloid leukemia.
PG  - 107437
LID - S1567-5769(21)00073-4 [pii]
LID - 10.1016/j.intimp.2021.107437 [doi]
AB  - Chemotherapy is the main treatment for acute myeloid leukemia (AML), but the 
      therapeutic efficacy is modest, and most commonly manifests as relapse from 
      remission. Thus, improving long-term AML survival is a crucial clinical 
      challenge. In recent years, oncolytic virotherapy has provided an alternative 
      approach for AML treatment. The use of oncolytic reoviruses has been explored in 
      more than 30 clinical trials for safety and feasibility issues. However, like 
      other oncolytic viruses, neutralizing antibodies (NAbs) reduce therapeutic 
      efficacy. To tackle this problem, human umbilical cord mesenchymal stem cells 
      (hUC-MSCs) were used to deliver reovirus using in vitro and in vivo models. Human 
      UC-MSCs were successfully loaded with reovirus, without impairing biological 
      function.We also observed in vitro protective effects of hUC-MSCs on reovirus in 
      the presence of NAbs. In the immunocompromised AML mouse model, hUC-MSCs 
      effectively carried reoviruses to tumor lesions and significantly prolonged the 
      survival of AML xenografts in mice in the presence of a high titer anti-reovirus 
      antibody (p = 0.001). However, reovirus-induced activation of AKT, 
      stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and NF-kappaB 
      signaling led to the maintenance of intrinsic migratory properties and secretion 
      of pro-inflammatory cytokines from hUC-MSCs, particularly CXCL10. In 
      immuno-competent AML mice, MSCs carrying reovirus triggered immune responses, and 
      eventually inhibited tumor growth. Therefore, these results suggest that MSCs as 
      carriers of oncolytic reoviruses can enhance the antitumor efficacy of 
      virotherapy.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Wang, Xianyao
AU  - Wang X
AD  - Department of Immunology, College of Basic Medical Sciences, Guizhou Medical 
      University, Guiyang 550025, China; Center for Tissue Engineering and Stem Cell 
      Research , Guizhou Medical University, Guiyang 550004, China; Key Laboratory of 
      Adult Stem Cell Translational Research (Chinese Academy of Medical Sciences), 
      Guiyang 550004, China.
FAU - Yang, Yichen
AU  - Yang Y
AD  - Center for Tissue Engineering and Stem Cell Research , Guizhou Medical 
      University, Guiyang 550004, China.
FAU - Wang, Nianxue
AU  - Wang N
AD  - Department of Immunology, College of Basic Medical Sciences, Guizhou Medical 
      University, Guiyang 550025, China; Center for Tissue Engineering and Stem Cell 
      Research , Guizhou Medical University, Guiyang 550004, China.
FAU - Wu, Xijun
AU  - Wu X
AD  - Center for Tissue Engineering and Stem Cell Research , Guizhou Medical 
      University, Guiyang 550004, China; Key Laboratory of Adult Stem Cell 
      Translational Research (Chinese Academy of Medical Sciences), Guiyang 550004, 
      China.
FAU - Xu, Jianwei
AU  - Xu J
AD  - Center for Tissue Engineering and Stem Cell Research , Guizhou Medical 
      University, Guiyang 550004, China; Key Laboratory of Adult Stem Cell 
      Translational Research (Chinese Academy of Medical Sciences), Guiyang 550004, 
      China; Department of Pharmacology, Guizhou Medical University, Guiyang 550025, 
      China.
FAU - Zhou, Yanhua
AU  - Zhou Y
AD  - Center for Tissue Engineering and Stem Cell Research , Guizhou Medical 
      University, Guiyang 550004, China; Key Laboratory of Adult Stem Cell 
      Translational Research (Chinese Academy of Medical Sciences), Guiyang 550004, 
      China.
FAU - Zhao, Xing
AU  - Zhao X
AD  - Department of Immunology, College of Basic Medical Sciences, Guizhou Medical 
      University, Guiyang 550025, China; Center for Tissue Engineering and Stem Cell 
      Research , Guizhou Medical University, Guiyang 550004, China; Key Laboratory of 
      Adult Stem Cell Translational Research (Chinese Academy of Medical Sciences), 
      Guiyang 550004, China. Electronic address: xingzhao@gmc.edu.cn.
FAU - He, Zhixu
AU  - He Z
AD  - Department of Immunology, College of Basic Medical Sciences, Guizhou Medical 
      University, Guiyang 550025, China; Key Laboratory of Adult Stem Cell 
      Translational Research (Chinese Academy of Medical Sciences), Guiyang 550004, 
      China; Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, 
      Zunyi 563000, China. Electronic address: hzx@gmc.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210208
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Female
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*therapy
MH  - *Mesenchymal Stem Cells
MH  - *Oncolytic Virotherapy
MH  - Oncolytic Viruses
OTO - NOTNLM
OT  - Acute myeloid leukemia
OT  - Antitumor efficacy
OT  - CXCL10
OT  - Human umbilical cord mesenchymal stem cells
OT  - Oncolytic reovirus
OT  - Virotherapy
EDAT- 2021/02/12 06:00
MHDA- 2021/06/23 06:00
CRDT- 2021/02/11 20:12
PHST- 2020/12/31 00:00 [received]
PHST- 2021/01/21 00:00 [revised]
PHST- 2021/01/24 00:00 [accepted]
PHST- 2021/02/12 06:00 [pubmed]
PHST- 2021/06/23 06:00 [medline]
PHST- 2021/02/11 20:12 [entrez]
AID - S1567-5769(21)00073-4 [pii]
AID - 10.1016/j.intimp.2021.107437 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2021 May;94:107437. doi: 10.1016/j.intimp.2021.107437. Epub 
      2021 Feb 8.