Mouse diabetes treated with rat-grown organs
The proof-of-principle study shows how cells of one species can be grown inside the body of another – a technique that could one day help people awaiting transplants. Jana Howden reports.
The idea of using other species to grow our own organs might seem like a stray plotline from Mary Shelley’s Frankenstein, but researchers have shown cells from one species can be successfully grown in another and harvested for transplant.
Reporting in Nature, Hiromitsu Nakauchi from Stanford University in the US and colleagues grew pancreatic cells – which are critical for regulating blood glucose levels – in rats and transplanted them into diabetic mice. There, the cells maintained blood glucose levels for over a year.
Stem cell biochemist Jose Polo from Monash University in Australia, who was not involved in the work, notes that the idea of growing organs in another species isn’t new – after all, the same group generated a rat pancreas in a mouse in 2010.
But, he adds, “what is pretty new and encouraging is that they were able to transplant the pancreas back into the mouse and cure diabetes, completing a full circle”.
An increasing number of people rely on life-saving organ transplants to cure debilitating and fatal diseases. For instance, when medication is no longer able to stabilise the type I diabetes – which occurs when pancreatic cells that produce insulin are lost – many patients must turn to pancreatic cell transplants. But donors can be hard to come by, and tissue rejection remains a problem.
To bypass this issue, Nakauchi and colleagues looked to pluripotent stem cells. These cells are like a blank canvas; they can grow into any type of cell in the body. Better still, these tiny powerhouses have the potential to produce countless replacement cells.
The researchers began by genetically modifying early-stage rat embryos to lack Pdx1 – a gene vital for proper development of the rat pancreas.
Pluripotent stem cells from mice were then injected into a mass of embryonic rat cells that lacked Pdx1. This mouse-rat cell combination was then transferred into a surrogate rat mother.
Because the rats were unable to grow their own pancreas – as they were missing the Pdx1 gene – the pluripotent stem cells from the mice developed into a pancreas within the body of the developing rats.
This meant that the organ grew to the size of a normal rat pancreas, but was made up of mouse cells rather than rat cells.
The mouse-made, rat-grown pancreas was then harvested and its insulin-producing cells transplanted into the kidney of diabetic mice.
Each diabetic mouse received a single dose of 100 clusters of cells – roughly equating to 350,000 cells.
The result? The diabetic mice corrected and maintained their blood glucose levels for 370 days after the transplant, with immunosuppressants being used for only the first five days following the transplant.
The researchers wanted to make sure it was actually the transplanted cells that were fixing the problem. When they removed the kidney from the mice, blood glucose levels spiked, confirming that without the transplant, the mice would have continued to suffer from diabetes.
When it comes to human applications, Polo notes that there are ethical considerations to take into account regarding the use of human stem cells, but remains positive: “There is a lot of potential in this technology [and] it could fill a gap if all these controls are taken.”
Nakauchi and colleagues acknowledge that for humans to undergo a similar treatment, it would require “organ generation in animals closer to humans in size or in evolutionary distance”, listing sheep, pigs or non-human primates as potential targets. They’re hopeful that further research in the field could open up new avenues of creating transplantable human tissue.