Researchers in Denmark have successfully created organ-like intestinal structures from extra-embryonic endoderm cells—a breakthrough that could help advance the use of lab-grown cells in the study and treatment of disease.

For decades, scientists have attempted to mimic the path that stem cells follow to turn into organs in embryos, but coaxing such cells to properly develop in the lab has been difficult.  A number of recent studies have attempted to specifically make a gut from stem cells in a dish, says Martin Proks, a Ph.D. student and one of the primary authors of a new study from Novo Nordisk Foundation Center for Stem Cell Medicine at the University of Copenhagen (reNEW). “We have found a new way to do this, a way which follows different aspects of what happens in the embryo. Here, we found a new route that the embryo uses, and we describe the intermediate stage that different types of stem cells could use to make the gut and other organs.”

The researchers identified all the potential cells that were candidates to form organs associated with the digestive track, such as liver, pancreas, lung, and intestine, based on labelling them with a genetic marker. Analyzing this big data required  innovative new approaches to analysis that were developed in collaboration with physical scientists at the Niels Bohr Institute.

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The reNEW research team then looked at pluripotent stem cells and endoderm extra-embryonic stem cells. Extra-embryonic endoderm cells are a new stem cell line that the same research team described previously. Such cells contribute to the gut organs by being very important support cells that provide membranes, nourishment for the membranes and more.

Until recently, people assumed extra-embryonic endoderm cells helped the embryo develop and then disappeared. But previous work in the ReNEW lab found that they originate from a different part of the embryo than pluripotent stem cells.

The current study, published recently in Nature Cell Biology, identified an alternative route that extra-embryonic cells can use to make intestinal organs in the embryo.  “We then used these stem cells to generate intestinal organ-like structures in a dish. The findings suggest that both routes could work. Using the alternative route might help laboratory grown cells form functional cells and treat and study disease,” says Michaela Rothova, one of the other principle authors on the study.

The discovery could prove to be an important one, as scientists for long have been trying to crack the code on how to develop stem cells into the correct cells needed for a specific treatment, test drugs or model a disease.

“We haven’t quite gotten there in terms of function, and we have problems maturing these cells. So perhaps we can solve some of these problems by trying this alternative route or by combining the alternative route with the traditional route,” adds Joshua Brickman, also of reNEW.