Scientists have advanced the possibility of producing human transplantable tissue for the treatment of type 1 diabetes, after successfully reversing the condition in mice transplanted with cells from rat-grown pancreases.
Researchers from Stanford University Medical Center in Palo Alto, CA, and the University of Tokyo in Japan reveal how they transplanted functional, insulin-producing cells grown in rats into mice with type 1 diabetes.
Dr. Hiromitsu Nakauchi, of the Department of Genetics at Stanford, and colleagues recently reported their findings in the journal Nature.
For more than 1 year after transplantation, the blood glucose levels of the mice were normalized.
Furthermore, the rodents only required 5 days of immunosuppressant treatment in order to prevent the transplanted cells from being rejected.
Type 1 diabetes is an autoimmune condition whereby the body attacks and destroys the islet cells of the pancreas. These are cells that produce the hormone insulin, which helps to regulate blood sugar levels.
Without insulin, blood sugar levels become too high. If left untreated, high blood sugar can increase the risk of numerous complications, including stroke, heart disease, kidney disease, and eye problems.
Type 1 diabetes can be managed through regular blood glucose monitoring, diet, insulin therapy, and other medications. However, there is currently no cure for the disease.
In recent years, researchers have investigated interspecies transplantation for the long-term treatment of type 1 diabetes – that is, growing an organ in one animal and transplanting it into another.
In a previous study, Dr. Nakauchi and colleagues successfully grew rat pancreases in mice. Though the organs were functional, the team notes that they only grew to the size of a mouse pancreas.
As such, when the organs were transplanted into rats with type 1 diabetes, they were not large enough to reverse the condition.
For the new study, the researchers took a different approach. They grew mouse pancreases in rats.
Firstly, the team implanted pluripotent stem cells from mice into the early embryos of rats. Pluripotent stem cells have the ability to form any other cell or tissue.
As a result of genetic engineering, the rats did not have the ability to develop their own pancreas, meaning they had to depend on the implanted stem cells for pancreatic development.
When the rats were fully grown, the researchers found that, unlike in the previous study, the majority of the pancreases had grown to the usual size of a rat pancreas.
The team then transplanted 100 insulin-producing islets from the rat pancreases into mice with type 1 diabetes. The researchers note that the mice were genetically matched to the stem cells that led to pancreatic formation.
They found that the islet transplantation led to normalized blood sugar levels in the mice for more than 370 days.
“Furthermore,” says Dr. Nakauchi, “the recipient animals only needed treatment with immunosuppressive drugs for 5 days after transplantation, rather than the ongoing immunosuppression that would be needed for unmatched organs.”
In a subgroup of the mice, the team removed and analyzed the islet cells to see whether they contained any rat cells. They found that the immune system of the mice had eradicated rat cells from the islet cells.
“This is very promising for our hope to transplant human organs grown in animals because it suggests that any contaminating animal cells could be eliminated by the patient’s immune system after transplant,” notes Dr. Nakauchi.
Additionally, the researchers saw no evidence of abnormalities caused by the stem cells that formed the islet cells, such as tumor formation.
The team notes that because pluripotent stem cells have high developmental plasticity, the likelihood of them forming tumors is high. The researchers speculate that the lack of tumor formation in this study is down to the fact that the stem cells were steered toward pancreatic development in rat embryos, rather than being encouraged to form islet cells in a lab dish.
Overall, the researchers believe their findings indicate that interspecies transplantation could become a feasible treatment option for type 1 diabetes in humans, though the authors note that the procedure would “require organ generation in animals closer to humans in size or in evolutionary distance such as sheep, pigs, or non-human primates.”
The authors add:
“As suggested by our study, islets generated in this manner appear functionally and immunologically identical to primary host islets.
Generation of human islets in this manner will enable direct comparison between such islets and islets generated through ‘standard’ in vitro directed differentiation and/or tissue engineering approaches in achieving clinically important therapeutic endpoints.”
However, the team stresses that much more research is required, and that there are a number of ethical concerns that should be addressed when it comes to transplanting human stem cells into the embryos of animals.