In a milestone achievement for better understanding the development and function of the human placenta, scientists have derived and grown trophoblast stem cells for the first time.
"Trophoblast cells play an essential role in the interactions between the fetus and mother," wrote senior author. These cells form the outer layer of the blastocyst, which eventually develops into an embryo and into a fetus. Trophoblast cells become the placenta, providing nutrients to the fetus and taking away waste.
Too few or too many trophoblast cells can mean disaster for the fetus and mother. An imbalance of trophoblast cells can lead to miscarriage in early pregnancy, or preeclampsia and other conditions later on. That is why it is important to study human trophoblast development and function, wrote senior author. "In our paper, our goal was to establish human trophoblast stem cells [as a tool for future study]."
The researchers derived trophoblast stem cells from human volunteers with approval from the Ethics Committee. The cells were then transferred to a growth medium to proliferate, but the cells died off.
Using genetic sequencing, the team found that the cells needed certain proteins activated and others inhibited to stay alive and maintain the same characteristics they would have in utero.
Authors show that activation of Wingless/Integrated (Wnt) and EGF and inhibition of TGF-β, histone deacetylase (HDAC), and Rho-associated protein kinase (ROCK) enable long-term culture of human villous cytotrophoblast (CT) cells.
The resulting cell lines have the capacity to give rise to the three major trophoblast lineages, which show transcriptomes similar to those of the corresponding primary trophoblast cells. Importantly, equivalent cell lines can be derived from human blastocysts.
Other cultured cell lines have been used as models of human trophoblast cells, yet those cells have drastically different protein expression than native trophoblast cells. Such differences could make it more difficult to determine disease origin or potential therapeutic targets.
"Our culture system for human trophoblast stem cells is potentially useful for understanding the pathogenesis of developmental disorders with trophoblast defects, such as miscarriage, preeclampsia and intrauterine growth restriction," senior author wrote, adding that the research team hopes the tool will be used for medical science, especially in the fields of etiology and new drug development to treat perinatal disease.