PMID- 23702186
OWN - NLM
STAT- MEDLINE
DCOM- 20140123
LR  - 20181203
IS  - 1532-3102 (Electronic)
IS  - 0143-4004 (Linking)
VI  - 34
IP  - 8
DP  - 2013 Aug
TI  - Influence of ischemic microenvironment on human Wharton's Jelly mesenchymal 
      stromal cells.
PG  - 642-9
LID - S0143-4004(13)00218-X [pii]
LID - 10.1016/j.placenta.2013.04.021 [doi]
AB  - INTRODUCTION: While in vivo studies suggest poor survival of mesenchymal stromal 
      cells (MSCs) after transplantation in ischemic conditions, in vitro studies 
      report diverse effects on proliferation, apoptosis and differentiation of 
      stem/precursor cells of different tissue-origin. The present focus is to 
      understand the influence of ischemic microenvironment on the survival, 
      proliferation, apoptosis, ROS-generation, antioxidant levels, 
      immunophenotypic-expression and neurotrophic factor secretion of Wharton's Jelly 
      (WJ)-MSCs. METHOD: WJ-MSCs were cultured in normoxic and hypoxic conditions in 
      presence and absence of serum and the end-point parameters were measured at 4 
      time-points. Cell survival, proliferation, apoptosis, ROS-generation and 
      immunophenotypic-expression were quantitatively detected either by fluorimetry or 
      flow cytometry techniques. ELISA-based methods were used for detection of 
      antioxidant-substrate glutathione (GSH) and neurotrophic factors [vascular 
      endothelial factor (VEGF), hepatocyte growth factor (HGF) and brain-derived 
      neurotrophic factor (BDNF)]. Expression of the antioxidants glutathione 
      peroxidase (GPx) and superoxide dismutase 1 (SOD1), was measured by real-time 
      RT-PCR. RESULT: Immunophenotypic analysis showed reduction in mesenchymal-marker 
      (CD73, CD90, and CD105) expression under ischemic conditions influenced mainly by 
      hypoxia, whereas the decrease in cell-survival under ischemic condition was 
      mainly as a result of nutrition depletion. This was associated with increased 
      ROS-generation and apoptosis and reduction in antioxidants (GSH, GPx, SOD1). For 
      neurotrophic factors, ELISA-readings showed that VEGF and HGF secretion (which 
      were higher in hypoxia) peaked at 48 h and decreased from 72 h, though BDNF 
      release did not decrease. DISCUSSION: Therapeutic benefits rendered by WJ-MSCs in 
      in vitro ischemic microenvironment are highest at the 48 h time-point, declining 
      thereafter with time probably due to failure in cellular defense systems and the 
      onset of apoptosis. CONCLUSION: It is hence clear that the growth factor 
      deficiency is more lethal to the cells than hypoxia in ischemic microenvironment.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Majumdar, D
AU  - Majumdar D
AD  - Manipal Institute of Regenerative Medicine, Manipal University, Bangalore, 
      Karnataka, India.
FAU - Bhonde, R
AU  - Bhonde R
FAU - Datta, I
AU  - Datta I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130520
PL  - Netherlands
TA  - Placenta
JT  - Placenta
JID - 8006349
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HGF protein, human)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (SOD1 protein, human)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 1.11.1.9 (Glutathione Peroxidase)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
SB  - IM
MH  - Apoptosis
MH  - Brain-Derived Neurotrophic Factor/biosynthesis
MH  - Cell Differentiation
MH  - Cell Hypoxia/*physiology
MH  - Cell Proliferation
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Glutathione Peroxidase/biosynthesis
MH  - Hepatocyte Growth Factor/biosynthesis
MH  - Humans
MH  - Ischemia/*physiopathology
MH  - Mesenchymal Stem Cells/*metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/biosynthesis
MH  - Superoxide Dismutase-1
MH  - Vascular Endothelial Growth Factor A/biosynthesis
MH  - Wharton Jelly/*cytology
EDAT- 2013/05/25 06:00
MHDA- 2014/01/24 06:00
CRDT- 2013/05/25 06:00
PHST- 2012/11/30 00:00 [received]
PHST- 2013/04/13 00:00 [revised]
PHST- 2013/04/30 00:00 [accepted]
PHST- 2013/05/25 06:00 [entrez]
PHST- 2013/05/25 06:00 [pubmed]
PHST- 2014/01/24 06:00 [medline]
AID - S0143-4004(13)00218-X [pii]
AID - 10.1016/j.placenta.2013.04.021 [doi]
PST - ppublish
SO  - Placenta. 2013 Aug;34(8):642-9. doi: 10.1016/j.placenta.2013.04.021. Epub 2013 
      May 20.