Mouse pancreas grown in rat then transplanted back 'cures' diabetes

Scientists have shown that it is possible to grow the organs of one animal species in the body of another and to transplant them successfully. In their research, mice pancreatic islets were grown inside rats, before being successfully transplanted into other, diabetic mice.

There is a global shortage of human organs available for transplantation. One solution would be to grow human organs in animals, although this is at present technically challenging and would raise a number of ethical questions.

Diabetes is one of the conditions that could benefit from such a strategy. The disease is characterised by abnormally high glucose levels in the blood. It occurs when not enough insulin is produced by the pancreas.

More specifically, insulin production takes place in clusters of cells known as pancreatic islets. For some patients with type 1 diabetes, for whom medicines have not worked, islet transplantation can be considered an interesting therapy. However, the shortage of organ donors means that it can be impossible for doctors to offer this therapeutic option.

This study, published in the journal Nature, is a proof-of-principle study that demonstrates that inter-species organ generation could one day potentially aid the production of transplantable human tissue and organs.

From mice to rats

In 2010, the authors, from Stanford University, California, had already successfully grown a rat pancreas in a mouse. However, the organ grew to only the size of a mouse pancreas, which meant that it was not big enough to be transplanted into a much larger rat.

So they tried the experiment the other way around – growing a mouse pancreas into a rat. They used mice pluripotent stem cells, which can differentiate into any cell types in the body, and injected these stem cells into rat embryos.

The stem cells mixed with the rat embryonic cells and together proliferated and differentiated. This led to the creation of a chimera – the resulting individual was a rat with almost all organs and tissues comprising rat and mouse cells.

The exception was the pancreas. Because the researchers had done a genetic manipulation to suppress the growth of the rat pancreas in the embryo, the pancreas was made up entirely of mouse cells. There was no need for long-term immuno-suppressive drugs to be given to the mice to avoid transplant rejection.

Many questions left unresolved

The second stage of the experiment was to transplant pancreatic islets in mouse models of type 1 diabetes – with no native β-cells, the cells in pancreatic islets that produce insulin. The researchers found out that the islets survived and were able to replace the native β-cells. Insulin was produced and blood-sugar levels remained normal for more than a year, indicating that the transplant was successful.

While these are impressive results, which prove that inter-species organ generation could be a good strategy to address the global shortage of organ donors, they open-up a series of pressing questions.

First, it is not certain that it would be technically feasible in humans and human applications are a long way off. Mice and rats are very closely related species with a similar genetic make-up. It might not be possible to use this strategy to grow organs in more distantly related species, such as would be the case with growing human organs in another animal.

Additionally, pancreatic islets are relatively small to transplant and the pancreas is far from being the more complex organ in the body. The real difficulty would be in growing more-complex organs such as the kidney or the heart can be grown in a similar way, as they are formed from many different progenitor cell types.

Beyond these technical issues, important debates around ethics will be needed before we can think of applying such methods to humans. Before anything happens, we would have to consider whether we can really use animals to grow our organs and to create 'human-animal chimera' and how safe this may be.