A mini-model of a human placenta can now be grown in the lab, which researchers say is a “transformative” step for investigating early stage pregnancy and how it can go wrong.
“The placenta is the first organ that the baby makes. It is a vital organ that connects the baby to the mother and is responsible for nourishing and protecting the baby while it is in the uterus,” says Margherita Turco, a research fellow at Cambridge University and first author of this study.
Many pregnancies fail because the embryo does not form a successful placental connection to the mother’s uterus. When something goes wrong with the placenta, this can have detrimental effects for both the mother and the baby. “Even after the baby is born, if the placenta was not functioning properly, that baby has higher susceptibility to diseases later on in life,” Turco explains.
Despite its importance in pregnancy, knowledge of the human placenta is limited. This is because, until now, scientists have relied on animal models, small placental samples or even just cells taken from a placenta. But these techniques can fail to accurately represent a real human placenta or do not survive for sufficiently long to enable a thorough and relatistic study.
Now, in a paper published in the journal Nature, a team of scientists from the Centre for Trophoblast Research at Cambridge University have announced a transformative development. They can grow mini-placentas - otherwise known as “placental organoids” - in the lab.
Simply put, an organoid is a miniaturised, simplified version of an organ that can be grown in the petri dish. With carefully defined conditions, a few cells will grow and arrange themselves into a three-dimensional structure that resembles the organ of choice. But the key to an organoid is that it shows at least some of the same behaviour as the real organ.
Turco and her team have found that their placental organoids are stable for long periods of time and have even been able to keep them alive for as long as a year. They also behave very like the real human placenta. For example, the organoids include all the main types of cells specifically found in a placenta and also produce placenta-specific hormones.
“One of the main functions of the placenta is to produce these hormones and proteins, which then signal to the mother. In our placenta organoids we could detect [the hormone] hCG, which is the first signal that the embryo produces, to signal to the mother that she is pregnant. And, in fact, it is what you detect on a pregnancy stick!”
The development of the placenta organoid has taken decades. One major challenge the team had to overcome was that while testing different conditions, they consistently observed growth of cells that didn’t seem quite right and that was because, as they realised later, they were growing cells from the mother’s uterus rather than from the placenta. It was after a lot of trial and error that the team in Cambridge have now been able to identify the optimal conditions for growing a placenta organoid.
In addition to this recent discovery, last year, the same team reported that they were able to grow organoids of the uterus lining. “Now we have organoids of both sides, so the placenta and the uterus, and we think this is going to be really transformative in trying to understand this communication that occurs between the placenta and the uterus,” says Turco.
“There is evidence that, at the beginning, the placenta is really dependent on secretions from the uterus in order for it to grow, but we don’t know what the natures of those secretions are and so it would be really interesting to see what is this dialogue between the placenta and the uterus.”
As well as opening up the possibility of studying in detail how the placenta grows and develops, the placenta organoids could also help to reveal other mysteries of early stage pregnancy. For example, some infections, like Zika, are able to pass from the mother’s blood to the fetus, but is the placenta able to prevent other infections from passing across?
Perhaps in the future placenta organoids will also offer a promising platform for testing the safety of new drugs during pregnancy. Overall it seems clear that these placenta organoids offer far-reaching possibilities for future research, from basic science to medical applications.
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