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Heart transplants are hard to come by, but based on the results of two papers published this week, we might one day be able to grow all the organs we need!

Hosted by: Hank Green
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Hank: It’s been an important week for the future of organ transplants. Like, game-changingly important.

In one paper, published on Wednesday in the journal Nature, a group of biologists announced that they’d genetically engineered a rat to grow a mouse’s pancreas, then successfully used cells from that pancreas to suppress diabetes in mice.

And in another paper, published on Thursday in the journal Cell, a different group announced that they’d genetically engineered a pig embryo to grow with some human cells.

There’s a long way to go before we’re able to grow functional human organs inside other animals. But both of these studies mean that we’re a lot closer.

Right now, the organs used in transplants have to come from human donors. But the donor pool isn’t very big, especially for essential organs like hearts and lungs that can only be donated when someone dies. It’s hard to find a match within that pool, and even if you can, the waiting list can be very long.

That’s why lots of researchers are looking into ways to grow human organs inside of other animals, so doctors could grow whatever healthy, functional organs they need. The same team that published the Nature paper this week actually created the first combined rat-mice, back in 2010.

Any animal with a mix of cells with different genes is known as a chimera, and these were the first rat-mouse chimeras to be grown from embryos and survive. To do this they injected rat stem cells into mouse embryos that had been genetically engineered so none of the mouse stem cells could develop into pancreatic tissue. Those embryos grew into rat-mouse chimeras, with mixtures of rat and mouse cells throughout their bodies except for their pancreases, because only the rat stem cells could grow into pancreatic tissue.

That was a big deal on its own, but originally, the researchers also wanted to try transplanting clusters of the pancreas cells, called islets, into rats to suppress type I diabetes. Islets produce the insulin that helps regulate blood sugar. But in type I diabetes, the immune system destroys the islets.

The researchers were hoping to transplant new islets into rats with type I diabetes to get them to start producing insulin again. The problem was, the pancreases were mouse-sized, so they weren’t big enough for the researchers to get all the islets they needed for a successful transplant. For the study published this week, the team tried the opposite of their 2010 experiment: they injected mouse stem cells into rat embryos. And these embryos grew into mouse-rat chimeras with pancreases that were fully mouse.

This time, the pancreases were rat-sized, so the researchers were able to get enough islets to perform transplants. They took islets from the mouse pancreases grown in the chimeras and transplanted them into mice with type I diabetes, so the mice started producing insulin again and the disease was suppressed.

When it comes to organs, the pancreas is relatively simple, so this isn’t quite the same as growing and transplanting, say, an entire heart or lung. That would be much more complicated. But thanks to this research, we now know that organ transplants from chimeras can actually work.

That’s just mice and rats, though. The goal of this line of research is to eventually grow human organs inside a species with similar-sized organs, like a pig or cow. And that’s where the paper published in Cell comes in.

This group of researchers wanted to create human-pig chimeras by injecting human stem cells into pig embryos. But that’s a lot harder than creating a rat-mouse chimera. For one thing, humans and pigs have much less DNA in common than rats and mice. For another, pig fetuses only take about 16 weeks to develop, while human fetuses take 40 weeks. So human stem cells and pig stem cells develop at different rates.

All this makes it harder for human cells to survive and become a healthy, integrated part of a pig embryo. For this study, the researchers injected human stem cells into pig embryos, then implanted those embryos into female pigs. They let the fetuses develop for just 3 to 4 weeks, then euthanized them so they could analyze their cells in the lab. They found that the chimeras had developed with some human cells but not very many of them, and even fewer of them grew to a typical, healthy size.

The fetuses were mostly pig, with some human cells sprinkled in among the developing muscles and organs. But still, they did it: the researchers made the first human-pig chimeras. And they’re hoping that the process can be improved to the point where pigs can be grown with specific human tissues or entire organs.

There are lots of extra challenges involved in this kind of research though, and it is controversial. For instance, nobody wants people growing pigs with, like, human brains. And we’re a long way away from being able to do anything like that, but scientists researching chimeras are still being really careful about the kinds of experiments they try. And it’s possible that someday this research will lead us to being able to grow functional, vital organs that people need.

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