PMID- 23618405
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20220410
IS  - 1757-6512 (Electronic)
IS  - 1757-6512 (Linking)
VI  - 4
IP  - 2
DP  - 2013 Apr 25
TI  - Exosomes released by human umbilical cord mesenchymal stem cells protect against 
      cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro.
PG  - 34
LID - 10.1186/scrt194 [doi]
AB  - INTRODUCTION: Administration of bone marrow mesenchymal stem cells (MSCs) or 
      secreted microvesicles improves recovery from acute kidney injury (AKI). However, 
      the potential roles and mechanisms are not well understood. In the current study, 
      we focused on the protective effect of exosomes derived from human umbilical cord 
      mesenchymal stem cells (hucMSC-ex) on cisplatin-induced nephrotoxicity in vivo 
      and in vitro. METHODS: We constructed cisplatin-induced AKI rat models. At 24 h 
      after treatment with cisplatin, hucMSC-ex were injected into the kidneys via the 
      renal capsule; human lung fibroblast (HFL-1)-secreted exosomes (HFL-1-ex) were 
      used as controls. All animals were killed at day 5 after administration of 
      cisplatin. Renal function, histological changes, tubular apoptosis and 
      proliferation, and degree of oxidative stress were evaluated. In vitro, rat renal 
      tubular epithelial (NRK-52E) cells were treated with or without cisplatin and 
      after 6 h treated with or without exosomes. Cells continued to be cultured for 24 
      h, and were then harvested for western blotting, apoptosis and detection of 
      degree of oxidative stress. RESULTS: After administration of cisplatin, there was 
      an increase in blood urea nitrogen (BUN) and creatinine (Cr) levels, apoptosis, 
      necrosis of proximal kidney tubules and formation of abundant tubular protein 
      casts and oxidative stress in rats. Cisplatin-induced AKI rats treated with 
      hucMSC-ex, however, showed a significant reduction in all the above indexes. In 
      vitro, treatment with cisplatin alone in NRK-52E cells resulted in an increase in 
      the number of apoptotic cells, oxidative stress and activation of the p38 
      mitogen-activated protein kinase (p38MAPK) pathway followed by a rise in the 
      expression of caspase 3, and a decrease in cell multiplication, while those 
      results were reversed in the hucMSCs-ex-treated group. Furthermore, it was 
      observed that hucMSC-ex promoted cell proliferation by activation of the 
      extracellular-signal-regulated kinase (ERK)1/2 pathway. CONCLUSIONS: The results 
      in the present study indicate that hucMSC-ex can repair cisplatin-induced AKI in 
      rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis, 
      promoting cell proliferation in vivo and in vitro. This suggests that hucMSC-ex 
      could be exploited as a potential therapeutic tool in cisplatin-induced 
      nephrotoxicity.
FAU - Zhou, Ying
AU  - Zhou Y
FAU - Xu, Huitao
AU  - Xu H
FAU - Xu, Wenrong
AU  - Xu W
FAU - Wang, Bingying
AU  - Wang B
FAU - Wu, Huiyi
AU  - Wu H
FAU - Tao, Yang
AU  - Tao Y
FAU - Zhang, Bin
AU  - Zhang B
FAU - Wang, Mei
AU  - Wang M
FAU - Mao, Fei
AU  - Mao F
FAU - Yan, Yongmin
AU  - Yan Y
FAU - Gao, Shuo
AU  - Gao S
FAU - Gu, Hongbing
AU  - Gu H
FAU - Zhu, Wei
AU  - Zhu W
FAU - Qian, Hui
AU  - Qian H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130425
PL  - England
TA  - Stem Cell Res Ther
JT  - Stem cell research & therapy
JID - 101527581
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
CIN - Stem Cell Res Ther. 2013;4(2):39. PMID: 23680102
MH  - Acute Kidney Injury/chemically induced/pathology/therapy
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Caspase 3/metabolism
MH  - Cell Differentiation
MH  - Cells, Cultured
MH  - Cisplatin/*toxicity
MH  - Exosomes/*metabolism
MH  - Female
MH  - Humans
MH  - Kidney Tubules/drug effects/metabolism/pathology
MH  - Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/*cytology
MH  - Oxidative Stress/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transplantation, Heterologous
MH  - Umbilical Cord/*cytology
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC3707035
EDAT- 2013/04/27 06:00
MHDA- 2015/03/31 06:00
PMCR- 2013/04/25
CRDT- 2013/04/27 06:00
PHST- 2012/11/02 00:00 [received]
PHST- 2013/03/08 00:00 [accepted]
PHST- 2013/04/27 06:00 [entrez]
PHST- 2013/04/27 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
PHST- 2013/04/25 00:00 [pmc-release]
AID - scrt194 [pii]
AID - 10.1186/scrt194 [doi]
PST - epublish
SO  - Stem Cell Res Ther. 2013 Apr 25;4(2):34. doi: 10.1186/scrt194.