PMID- 37491116
OWN - NLM
STAT- MEDLINE
DCOM- 20230727
LR  - 20230727
IS  - 1879-3592 (Electronic)
IS  - 1383-5718 (Linking)
VI  - 889
DP  - 2023 Jul
TI  - Mesenchymal stem cell-derived exosomes attenuate DNA damage response induced by 
      cisplatin and bleomycin.
PG  - 503651
LID - S1383-5718(23)00069-4 [pii]
LID - 10.1016/j.mrgentox.2023.503651 [doi]
AB  - Stem cell-derived exosomes (SC-Exos) have been shown to protect cells from 
      chemical-induced deoxyribonucleic acid (DNA) damage. However, there has been no 
      systematic comparison of the efficacy of exosomes against different types of DNA 
      damage. Therefore, in this study, we assessed the protective effect of exosomes 
      derived from human embryonic stem cell-induced mesenchymal stem cells 
      (hESC-MSC-Exos) on two types of DNA damage, namely, intra-/inter-strand 
      crosslinks and DNA double-strand breaks induced by cisplatin (Pt) and bleomycin 
      (BLM), respectively, in HeLa cells. The alkaline comet assay demonstrated that 
      hESC-MSC-Exos effectively inhibited Pt- and BLM-induced DNA damage in a 
      dose-dependent manner. When the concentration of hESC-MSC-Exos reaches 
      2.0 x 10(6) and 4.0 x 10(6) particles/mL in Pt- and BLM-treated groups, 
      respectively, there was a significant decrease in tail DNA percentage (Pt: 
      20.80 +/- 1.61 vs 9.40 +/- 1.14, p < 0.01; BLM: 21.80 +/- 1.31 vs 6.70 +/- 0.60, 
      p < 0.01), tail moment (Pt: 10.00 +/- 1.21 vs 2.08 +/- 0.51, p < 0.01; BLM: 
      12.00 +/- 0.81 vs 2.00 +/- 0.21, p < 0.01), and olive tail moment (Pt: 6.01 +/- 0.55 vs 
      2.09 +/- 0.25, p < 0.01; BLM: 6.03 +/- 0.37 vs 1.53 +/- 0.13, p < 0.01). 
      Phospho-histone H2AX (gammaH2AX) immunofluorescence and western blotting showed an 
      over 50 % decrease in gammaH2AX expression when the cells were pretreated with 
      hESC-MSC-Exos. As reactive oxygen species (ROS) are important mediators of Pt- 
      and BLM-induced DNA damage, dichloro-dihydro-fluorescein diacetate staining 
      indicated that hESC-MSC-Exos inhibited the increase in intracellular ROS in 
      drug-treated cells. In conclusion, our findings suggest that hESC-MSC-Exos can 
      protect cells from the two types of DNA-damaging drugs and that reduced 
      intracellular ROS is involved in this effect.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Hu, Xiaoqiang
AU  - Hu X
AD  - Department of Occupational and Environmental Health, Hangzhou Normal University 
      School of Public Health, Hangzhou 311121, China.
FAU - He, Chuncao
AU  - He C
AD  - Department of Nutrition and Toxicology, Hangzhou Normal University School of 
      Public Health, Hangzhou 311121, China.
FAU - Zhang, Lijun
AU  - Zhang L
AD  - Department of Nutrition and Toxicology, Hangzhou Normal University School of 
      Public Health, Hangzhou 311121, China.
FAU - Zhang, Yunheng
AU  - Zhang Y
AD  - Department of Nutrition and Toxicology, Hangzhou Normal University School of 
      Public Health, Hangzhou 311121, China.
FAU - Chen, Liangjing
AU  - Chen L
AD  - Department of Occupational and Environmental Health, Hangzhou Normal University 
      School of Public Health, Hangzhou 311121, China.
FAU - Sun, Chuan
AU  - Sun C
AD  - Zhejiang Provincial Key Lab of Geriatrics & Geriatrics Institute of Zhejiang 
      Province, Department of Geriatrics, Zhejiang Hospital, Hangzhou 310030, China.
FAU - Wei, Jun
AU  - Wei J
AD  - State Key Laboratory of Cellular Stress Biology, Xiamen University School of Life 
      Sciences, Xiamen 361005, China.
FAU - Yang, Lei
AU  - Yang L
AD  - Department of Occupational and Environmental Health, Hangzhou Normal University 
      School of Public Health, Hangzhou 311121, China.
FAU - Tan, Xiaohua
AU  - Tan X
AD  - Department of Nutrition and Toxicology, Hangzhou Normal University School of 
      Public Health, Hangzhou 311121, China.
FAU - Yang, Jun
AU  - Yang J
AD  - Department of Nutrition and Toxicology, Hangzhou Normal University School of 
      Public Health, Hangzhou 311121, China; Center for Uterine Cancer Diagnosis and 
      Therapy Research, The Affiliated Women's Hospital, Zhejiang University School of 
      Medicine, Hangzhou 310006, China. Electronic address: gastate@zju.edu.cn.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Occupational and Environmental Health, Hangzhou Normal University 
      School of Public Health, Hangzhou 311121, China. Electronic address: 
      yanzhang@hznu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20230608
PL  - Netherlands
TA  - Mutat Res Genet Toxicol Environ Mutagen
JT  - Mutation research. Genetic toxicology and environmental mutagenesis
JID - 101632149
RN  - Q20Q21Q62J (Cisplatin)
RN  - 0 (Reactive Oxygen Species)
SB  - IM
MH  - Humans
MH  - *Exosomes/metabolism
MH  - Cisplatin/toxicity
MH  - HeLa Cells
MH  - Reactive Oxygen Species/metabolism
MH  - *Mesenchymal Stem Cells
MH  - DNA Damage
OTO - NOTNLM
OT  - Cell viability
OT  - Conditioned medium
OT  - DNA adducts
OT  - Extracellular vesicles
OT  - Oxidative stress
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/07/26 01:06
MHDA- 2023/07/27 06:42
CRDT- 2023/07/25 20:53
PHST- 2022/12/16 00:00 [received]
PHST- 2023/06/01 00:00 [revised]
PHST- 2023/06/06 00:00 [accepted]
PHST- 2023/07/27 06:42 [medline]
PHST- 2023/07/26 01:06 [pubmed]
PHST- 2023/07/25 20:53 [entrez]
AID - S1383-5718(23)00069-4 [pii]
AID - 10.1016/j.mrgentox.2023.503651 [doi]
PST - ppublish
SO  - Mutat Res Genet Toxicol Environ Mutagen. 2023 Jul;889:503651. doi: 
      10.1016/j.mrgentox.2023.503651. Epub 2023 Jun 8.