PMID- 26824459
OWN - NLM
STAT- MEDLINE
DCOM- 20161025
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 38
IP  - 1
DP  - 2016
TI  - The Effects of Indoxyl Sulfate on Human Umbilical Cord-Derived Mesenchymal Stem 
      Cells In Vitro.
PG  - 401-14
LID - 10.1159/000438639 [doi]
AB  - BACKGROUND/AIMS: Indoxyl sulfate, an important protein-bound uremic toxin, can 
      damage stem cells, thus hampering stem cell-based regenerative medicine 
      approaches targeting chronic kidney diseases (CKD). Human umbilical cord-derived 
      mesenchymal stem cells (hUC-MSCs) are thought to have promising clinical 
      application because of their high proliferative potential and ease of isolation 
      than MSCs from other sources. In the present study, we aimed to determine the 
      harmful effects of indoxyl sulfate on the phenotype and functional potential of 
      hUC-MSCs in vitro. METHODS: The toxicity and cell viability was examined by 
      Trypan blue exclusion and MTT assay. The cellular surface markers and the 
      percentage of apoptotic cells by Annexin-V/PI staining were analyzed by flow 
      cytometry. Proliferation was evaluated based on cell number counting and Ki-67 
      immunostaining. Cell senescence was measured using senescence-associated 
      beta-Galactosidase activity. The ability to stimulate the development of 
      CD4+CD25+FoxP3+ regulatory T cells was assessed by incubating hUC-MSCs with 
      peripheral blood mononuclear cells from the healthy volunteers. RESULTS: Our 
      results demonstrated that the immunophenotype of hUC-MSCs was not affected by 
      indoxyl sulfate flow cytometry. However, a significant decrease in cell numbers 
      and fraction of Ki-67 positive proliferating cells, along with a significant 
      increase in cellular senescence were detected in hUC-MSCs after exposure to 
      indoxyl sulfate. Additionally, their ability to stimulate CD4+CD25+FoxP3+ 
      regulatory T cell production was compromised when hUC-MSCs were pretreated with 
      indoxyl sulfate. CONCLUSION: Taken together, our study clearly demonstrated that 
      the molecular alterations and functional incompetence in hUC-MSCs under the 
      challenge of indoxyl sulfate in vitro.
CI  - (c) 2016 The Author(s) Published by S. Karger AG, Basel.
FAU - Wang, Wei
AU  - Wang W
AD  - The Kidney Disease Research Center, Jingdong Yumei Kidney Disease Hospital, 
      Beijing, China.
FAU - Liu, Xueyong
AU  - Liu X
FAU - Wang, Wei
AU  - Wang W
FAU - Li, Jinghua
AU  - Li J
FAU - Li, Yuanyuan
AU  - Li Y
FAU - Li, Liping
AU  - Li L
FAU - Wang, Shaohua
AU  - Wang S
FAU - Zhang, Jianchun
AU  - Zhang J
FAU - Zhang, Youkang
AU  - Zhang Y
FAU - Huang, Haichang
AU  - Huang H
LA  - eng
PT  - Journal Article
DEP - 20160129
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Antigens, CD)
RN  - 0 (Ki-67 Antigen)
RN  - EC 3.2.1.23 (beta-Galactosidase)
RN  - N187WK1Y1J (Indican)
SB  - IM
MH  - Antigens, CD/metabolism
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cellular Senescence/drug effects
MH  - Humans
MH  - Immunophenotyping
MH  - Indican/*toxicity
MH  - Ki-67 Antigen/metabolism
MH  - Mesenchymal Stem Cells/cytology/*drug effects/metabolism
MH  - T-Lymphocytes, Regulatory/cytology/immunology/metabolism
MH  - Umbilical Cord/*cytology
MH  - beta-Galactosidase/metabolism
EDAT- 2016/01/30 06:00
MHDA- 2016/10/26 06:00
CRDT- 2016/01/30 06:00
PHST- 2015/12/07 00:00 [accepted]
PHST- 2016/01/30 06:00 [entrez]
PHST- 2016/01/30 06:00 [pubmed]
PHST- 2016/10/26 06:00 [medline]
AID - 000438639 [pii]
AID - 10.1159/000438639 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2016;38(1):401-14. doi: 10.1159/000438639. Epub 2016 Jan 
      29.