Conditioning of human embryonic stem cell‐derived endothelial cells with PBMCs confers TLR4 sensing in co‐culture conditions

• Published in: The FASEB journal 2013-04, Vol.27 (S1)
• Main Authors: Reed, Daniel Mark, Foldes, Gabor, Gashaw, Hime H, Harding, Sian E, Mitchell, Jane A
• Format: Article
• Language: English
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fasebj.27.1_supplement.lb614

Human embryonic stem cell‐derived endothelial cells (hESC‐EC) are being investigated as potential therapies for vascular disease. We have previously shown that hESC‐EC do not have functional Toll‐like receptor‐4 (TLR4) responses but do respond avidly to cytokines such as TNFα and IL‐1β1,2, which illustrates that these cells do have fully functional TLR signaling via MyD88 and NF‐κB. In this study we show that, whilst hESC‐EC do not respond to LPS (1μg/ml) to release CXCL8 when treated in mono‐culture, they mediate a synergy when co‐cultured with peripheral blood mononuclear cells (PBMCs). No synergy was found in co‐cultures stimulated with TNFα (10ng/ml) suggesting that the conditioning effects of PBMCs on hESC‐EC is above the level of NF‐κB and downstream pathways leading to CXCL8 release. This data is highly novel but preliminary and more studies need to be performed to establish how this conditioning effect is mediated. These findings will be significant in the use of hESC‐EC in vessel engineering and highlight the importance of cell interactions on stem cell and endothelial cell function. This work was funded by the Welcome Trust, BHF and an MRC studentship awarded to DMR.