Human-pig chimeras

In a pair of recent publications, scientists showed the following:

• Mouse pancreatic cells produced in a rat can cure diabetic mice
• Human stem cells can contribute to tissues in pig embryos (i.e. it’s possible to make human-pig chimeras)

In the future, scientists hope to combine these findings to determine if it’s possible to make human pancreatic cells in other animals. These cells could be used to treat diabetes.

What is a chimera?

You can check out the wikipedia chimera page for the description of a mythological chimera (essentially a beast consisting of a lion, goat, and snake). While cool, that’s not what we’re talking about here. In biology, a chimera is a single organism composed of genetically distinct cells.

We normally think that all the cells in an organism have the same DNA sequences. This is true most of the time. Yet, there are a few natural cases where cell’s change their DNA sequences (in the production of B cells for instance). In addition, humans can be born with patches of cells that have non-identical DNA (check out this Scientific American Article for more information).

Beyond these natural cases, scientists use stem cells to create chimeric organisms. To do so, they implant foreign stem cells into developing embryos.  These grow along with the embryo. Ultimately, they will make up some fraction of the cells in the adult.

Scientists routinely make chimeric mice composed of cells from genetically distinct mouse strains. Scientists use these chimeric mice to produce new strains with particular traits (see chimeric mouse image above).

It’s also possible to create chimeras between different species (like between mice and rats). However, it’s unclear how different the two species can be. Furthermore, while most would argue that creating chimeras within a single species is okay, it’s ethically questionable to produce chimeras with cells from different species.

You might ask – why make interspecies chimeras in the first place? The answer: chimeras may allow us to cure disease.

Indeed the combined results from two papers (one published in the journal Nature, the other in the journal Cell) show that it may be possible to use chimeras to grow replacement cells for those with diseases.

Growing a replacement pancreas for a mouse

The first paper showed that, if you take a rat embryo that’s unable to grow a pancreas and give it stem cells from a mouse , the mouse stem cells will form a pancreas in the rat. This rescues the developing rat which would otherwise die.

You can then take the pancreas cells from the rat and use them to replace broken cells in a diabetic mouse. This mouse will essentially be cured of its diabetes.

Now you might say, “Why grow a mouse pancreas in a rat? Couldn’t you just taken pancreas cells from another mouse?”

In the case of mice, you have a point. Scientists could easily harvest the necessary pancreas cells from another mouse. However, researchers would like to use similar techniques to cure human diabetes. You can’t just take one person’s pancreas cells and use them to treat a different person with diabetes. If, however, you can grow a human pancreas in another animal, you could potentially use it to treat diabetes.

Making human-pig chimeras

The second paper set out to determine if human stem cells can contribute to embryos of other animals (specifically pigs). TLDR – Yes, the process is inefficient and requires the stem cells to be prepared in a particular way, but it does work.

In this work, the researchers did not allow the chimeric pigs to fully develop. It’s unclear if they even could. Yet these results do provide evidence that it’s possible to grow human organs in pigs.

There are a number of important issues that need to be considered before similar research moves forward:

1. Ethics – We have to ask the question, should we be making chimeras to treat disease? In my mind, chimeras have two major ethical issues:
   • Unintended consequences: Just one example, we don’t have good ways of directing human stem cells to particular pig tissues yet. This raises questions like – If some of the human cells contribute to the pig’s brain, will that affect the pig’s cognition? What other attributes might the chimeric pig gain?
   • Animal welfare: What about the welfare of the pig? A pure utilitarian might argue that the ends, curing human disease, justify the means. However, there may be other ways to achieve the same goal. For example, should we focus our efforts on growing organs in the lab?
2. Human pancreas formation – The papers discussed above are very interesting and demonstrate important first steps towards the production of viable human-pig chimeras. However, these researchers did not show whether or not a fully grown pig could be formed using this technique. New techniques may be required for the creation of fully functional organs.
3. Immune rejection – In the mouse/rat experiments above, researchers suppressed the mouse immune system. As a result, the mice didn’t have drastic immune responses to the replacement pancreatic cells. If replacement human pancreatic cells were taken from a pig, how would the human immune system respond to them?

Final thoughts on chimeras in research

These are the 3 biggest challenges that I can think of at the moment. I’m sure there are many more, but these shouldn’t dissuade researchers from at least thinking about pursuing this work. Keep in mind that pig valves are already used to replace human heart valves. Pigs were also once a major source of insulin for Type I diabetes. In a way, human-pig chimeras have been around for a long time.