3 research outputs found
Evidence for bystander signalling between human trophoblast cells and human embryonic stem cells
Maternal exposure during pregnancy to toxins can occasionally lead to miscarriage and
malformation. It is currently thought that toxins pass through the placental barrier, albeit bilayered
in the first trimester, and damage the fetus directly, albeit at low concentration. Here we
examined the responses of human embryonic stem (hES) cells in tissue culture to two metals at low
concentration. We compared direct exposures with indirect exposures across a bi-layered model
of the placenta cell barrier. Direct exposure caused increased DNA damage without apoptosis or
a loss of cell number but with some evidence of altered differentiation. Indirect exposure caused
increased DNA damage and apoptosis but without loss of pluripotency. This was not caused by
metal ions passing through the barrier. Instead the hES cells responded to signalling molecules
(including TNF-α) secreted by the barrier cells. This mechanism was dependent on connexin 43
mediated intercellular âbystander signallingâ both within and between the trophoblast barrier and
the hES colonies. These results highlight key differences between direct and indirect exposure of hES
cells across a trophoblast barrier to metal toxins. It offers a theoretical possibility that an indirectly
mediated toxicity of hES cells might have biological relevance to fetal development