Using a mouse model, the researchers deciphered an alternative pathway that certain cells take to make organs and used this knowledge to harness a new type of stem cell as a potential source of organs in a dish.
Imagine if you could repair the damaged tissues of our organs. This is what stem cell research is aiming for, because stem cells have enormous potential to produce the cells of organs like the liver, pancreas and intestine.
For decades, scientists have tried to mimic the path taken by stem cells to form, for example, organs in embryos. However, despite considerable effort, getting the cells to grow properly in the lab has been very difficult. But they may have overlooked an important step and may have missed another type of stem cell, a new study from the University of Copenhagen suggests.
“Very simply, a number of recent studies have attempted to make a gut from stem cells in a dish. We’ve come up with a new way of doing it, a way that tracks different aspects of what’s going on in the embryo Here, we have found a new pathway that the embryo uses, and we describe the intermediate step that different types of stem cells could use to make the intestine and other organs,” says Ph.D. student at Martin Proks , one of the lead authors of the study from the Novo Nordisk Foundation Center for Stem Cell Medicine at the University of Copenhagen (reNEW).
The researchers looked at so-called pluripotent stem cells and extra-embryonic stem cells from the endoderm. Extra-embryonic endoderm cells are a new line of stem cells that the same research team described a few years ago. They contribute to the intestinal organs by being very important supporting cells that provide membranes, nourish the membranes and more.
Group leader and professor Joshua Brickman of reNEW explains:
“We have identified an alternative pathway that so-called extra-embryonic cells can use to make intestinal organs in the embryo. We then took our extra-embryonic endoderm stem cells and grew them into intestinal organ-like structures in the dish.
“But until very recently, people assumed that these cells helped the embryo to develop, and then they disappeared. That they have nothing to do with your body. So, in this paper, we discovered that if we direct these supporting cells through this novel alternative pathway, they would actually form organoid structures,” says Joshua Brickman of the findings, which were published in Natural Cell Biology.
Could improve cells grown in the lab
The researchers identified all potential candidate cells for forming organs associated with the digestive tract, such as the liver, pancreas, lungs and intestine, by labeling them with a genetic marker. This big data is difficult to analyze and required new innovative analytical approaches that were developed in collaboration with physicists from the Niels Bohr Institute.
“We then identified the genes used in these cells. To facilitate this work, we developed a new computational tool to compare clusters of cells and used it both to compare cells in our own dataset and to examine others,” says Associate Professor Ala Trusina at the Niels Bohr Institute.
In order to investigate whether the alternative pathway could grow organ cell types in the lab, the researchers set out to use a different type of stem cell. These stem cells, which were described earlier in the article, come from a different part of the embryo than pluripotent stem cells, and they look like the starting point of the second or alternative path of organ formation. .
“We then used these stem cells to generate structures resembling intestinal organs in a dish. The results suggest that both pathways could work. Using the alternative pathway could help cells grown in the lab to form functional cells and to treat and study disease,” says Michaela Rothova, one of the study’s other lead authors.
This could prove to be an important discovery, as scientists have long been trying to crack the code on how to grow stem cells into the correct cells needed for a specific treatment, testing drugs or modeling disease.
“We’re not there yet in terms of function, and we’re having issues maturing these cells. So maybe we can solve some of these problems by trying this alternative route or combining the alternative route with the traditional route,” concludes Joshua Brickman of reNEW.