Cord blood mesenchymal stromal cell-conditioned medium protects endothelial cells via STAT3 signaling

Cell Physiol Biochem. 2014;34(3):646-57. doi: 10.1159/000363030. Epub 2014 Aug 13.


Background/aims: Cell-based therapies may be useful for treating ischemic diseases, but the underlying mechanisms are incompletely understood. We investigated the impact of cord blood mesenchymal stromal cell (CBMSC)- or fibroblast (FB)-secreted factors on starved endothelial cells and determined the relevant intracellular signaling pathways.

Methods: HUVECs were subjected to glucose/serum deprivation (GSD) in hypoxia or normoxia, in presence of CBMSC- or FB-conditioned medium (CM). Viability and proliferation were determined via WST-8 conversion and BrdU incorporation. Apoptosis was quantified by annexin V/ethidium homodimer-III staining, nuclear fragmentation and cell morphology. mRNA expression and protein phosphorylation were determined by real-time qPCR and western blot. Experiments were repeated in presence of small-molecule inhibitors.

Results: The negative impact of GSD was most pronounced at 21% O2. Here, medium of CBMSCs and FBs increased viability and proliferation and reduced apoptosis of HUVECs. This was associated with increased STAT3 and ERK1/2 phosphorylation and BCL-2 expression. Under STAT3 inhibition, the beneficial effect of CBMSC-CM on viability and BCL-2 expression was abolished.

Conclusion: Factors released by CBMSCs protect endothelial cells from the deleterious impact of GSD by activation of the STAT3 survival pathway. However, this phenomenon is not CBMSC-specific and can be reproduced using juvenile fibroblasts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Base Sequence
  • Culture Media, Conditioned*
  • DNA Primers
  • Fetal Blood / cytology*
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Real-Time Polymerase Chain Reaction
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction*


  • Culture Media, Conditioned
  • DNA Primers
  • STAT3 Transcription Factor
  • STAT3 protein, human