[SciShow Intro]

Hank Green: Stem cells are widely believed to hold great promise in medical research because of their ability to transform into all sorts of other cell types, like blood, skin, nerve, and muscle cells. Scientists believe that understanding how stem cells work and figuring out how to hack their developmental process could lead to major advancements in all sorts of areas. But that is going to take a lot of rigorous research, which is why molecular biologists are working on better, more efficient ways of growing high-quality human stem cells for us to study. And it turns out, one solution could be growing human stem cells in living mice.

Right now, the best and most common way of growing cells for research purposes is through in vitro cell culture. In vitro is Latin for "in glass". Though more often these days we use a plastic vessel like a flask or a petri dish.

The good news is that we actually have roughly a century of experience cultivating plant, animal, and human cells in vitro. The bad news is that there are problems that come with culturing cells outside a living body. One issue is that it can be tough to get cells to grow well in vitro.

You need just the right mix of conditions for cells to thrive. Another issue is that when cells grow inside organisms, they're part of a complex system. They're surrounded by other cells and proteins and tissues in a three-dimensional environment.

But when you grow cells in a dish, you're often just culturing one type of cell in a monolayer, which is a single layer of cells that's anchored to the container it's grown in. And while you can grow cells in suspension, meaning not attached to a dish, it only works for certain types of cells. As a result, cell culture can cause problems when it comes to conducting accurate research.

Cells grown in vitro simply don't accurately mimic how cells behave inside an organism. So studies conducted in vitro may yield data that does not match up with what's really happening in a living subject. It's close enough for many applications, but it is far from perfect.

Of course, most stem cell research also relies on these in vitro methods. Unfortunately, that means these cells experience all these same issues we just talked about and more. Growing in culture can also interfere with their ability to differentiate into other types of cells.

And when it comes to culturing human stem cells, it's important that we get every detail right. Scientists are hoping that stem cell research will help us treat or even cure complicated conditions like Alzheimer's or Parkinson's disease. That's because both of these illnesses affect our body's neurons, which we don't really regenerate.

However, understanding and harnessing the regenerative abilities of stem cells could one day allow researchers to repair or replace damaged neurons. In particular, research focuses on pluripotent stem cells. Ones that have the ability to differentiate into most of the kinds of cells the cells the body makes.

And getting them to do that right requires stringent culture techniques. So what can we do to culture better human stem cells? The solution may be to use mice rather than culture dishes to grow our stem cells.

For instance, a 2016 study by researchers from the University of Cambridge injected human stem cells into mouse embryos to see if they would develop as the mouse did. The researchers found that more than 70% of the transplanted embryos did grow human stem cells. The study showed that human stem cells could potentially be grown in vivo, or in a living mouse, from the embryonic stage.

But in order to effectively grow human stem cells for research purposes, you have to grow a lot of them. But a 2020 study may have found the solution to that problem. In order to try and grow decent quantities of human pluripotent stem cells in mice, the researchers first had to figure out how to bump the cells back to their naive phase -- the earliest stage of pluripotency.

That's because mouse embryonic stems cells are also in the naive phase, while pluripotent stem cells have already moved onto the next phase of development, called the primed phase, where they're ready to commit to being a certain type of cell. And in order for the human stem cells to grow effectively, they needed to match the stage of the mouse embryo. So, in order to transform the primed stem cells into naive ones, the scientists injected primed cells with an inhibitor that would shut down the proteins responsible for making the cells develop.

Once the scientists had the newly naive stem cells ready, they transferred them into the mouse embryos that were 2 to 4 days old. When scientists analyzed the cells about 17 days later, they found that the human cells had multiplied. Cells derived from the original human pluripotent cells now accounted for 0.1% to 4% of the cells in each mouse embryo.

Considering the job of a mouse embryo is to create a mouse, not a human, that's a lot. Despite being inside a mouse, the stem cells had begun developing into different types of human cells, like liver, skin, and blood cells. And all this could be really helpful for biomedical research.

First, being able to grow stem cells in mice could help us create better mouse models for researching human diseases. We use mice already to study human diseases of course, but unfortunately mice don't actually get every human disease we want to study. And while we can genetically modify mice to mimic the symptoms of those diseases, it's not always as accurate as we'd hope.

But making mice more like humans might help close that gap. There's another huge benefit to figuring out how to grow human stem cells in mice: organ generation. If we can grow cells in non-human animals, it may be possible to grow functional human organs in them, too.

This is pretty promising from a scientific point of view, however there are ethical questions that scientists and the larger community will need to address. For instance, if these animals have human cells and human DNA, should we treat them differently than a normal lab animal? This method of growing cells in mice is not going to replace traditional cell culture, but growing our stem cells in mice could be one way to realize the promise they represent.

Thanks for watching this episode of Scishow and thanks to our perennial President of Space, SR Foxley, for helping us bring it to all of you. Your support makes a huge difference, so thanks. If you're interested in supporting Scishow as well, check out patreon.com/scishow. [SciShow Outro]