Researchers from the laboratory of Yosef (Yossi) Buganim at Hebrew University of Jerusalem have used genetic engineering techniques to directly reprogram mouse skin cells into stable, and fully functional placenta-generating cells called induced trophoblast stem cells (iTSCs).
The placenta forms a vital link between a mother and her baby. When the placenta does not work as well as it should, the baby will receive less oxygen and nutrients from the mother. Consequently, the baby might show signs of fetal stress (that is the baby’s heart does not work properly), not grow nearly as well, and have a more difficult time during labor. Such a condition is called “placental insufficiency” and it can cause recurrent miscarriages, low birth weight, and birth defects.
Placental dysfunction has also been linked to a condition called fetal growth restriction (AKA Intrauterine growth restriction). Intrauterine growth restriction or IUGR is a condition characterized by poor growth of a baby while in the mother’s womb during pregnancy.
How can scientists study the placenta? Virtually all attempts to grow placental cells in culture have been largely unsuccessful.
Buganim and his colleagues have solved this problem. A screen for genes that support the development of the placenta yielded three genes: GATA3, Eomes, and Tfap2c. Next the Buganim team took mouse skin fibroblasts and forced the expression of these three placenta-specific genes in them. This initiated a cascade of events in the cells that converted them into stable and fully functional placenta-generating cells.
These skin-derived TSCs behave and look like native TSCs and they also function and contribute to developing placenta. The Bugamin laboratory used mouse cells for these experiments, but they want to expand their experiments to include human cells to make human iTSCs.
The success of this study could potentially give women who suffer from recurrent miscarriage and placental dysfunction diseases the ability to have healthy babies. The embryo is not at risk from such cells, since iTSCs integrate into the placenta and not into the embryos itself.
See Cell Stem Cell. 2015 Sep 22. pii: S1934-5909(15)00361-6. doi: 10.1016/j.stem.2015.08.006.