Insulin producing islet cells grown in the pancreas of animals such as pigs or sheep could one day be transplanted into humans to treat diabetes, according to scientists.
Researchers report that islets from rat grown mouse pancreases have been successfully used to reverse diabetes with a minimum amount of immunosuppressive therapy to prevent rejection.
The scientists from Stanford University School of Medicine in the United States and the Institute of Medical Science at the University of Tokyo in Japan, believe that the success of the interspecies transplantation suggests that a similar technique could be used for humans.
They were particularly pleased that the research using rats and mice found that the recipient mice required only days of immunosuppressive therapy to prevent rejection of the genetically matched organ rather than lifelong treatment.
The researchers implanted mouse pluripotent stem cells, which can become any cell in the body, into early rat embryos. The rats had been genetically engineered to be unable to develop their own pancreas and were thus forced to rely on the mouse cells for the development of the organ.
Once the rats were born and grown, the researchers transplanted the insulin producing cells, which cluster together in groups called islets, from the rat grown pancreases into mice genetically matched to the stem cells that formed the pancreas. These mice had been given a drug to cause them to develop diabetes.
‘We found that the diabetic mice were able to normalize their blood glucose levels for over a year after the transplantation of as few as 100 of these islets,’ said Hiromitsu Nakauchi, professor of genetics at Stanford.
‘Furthermore, the recipient animals only needed treatment with immunosuppressive drugs for five days after transplantation, rather than the ongoing immunosuppression that would be needed for unmatched organs,’ he added.
The transplantation of functional islets from healthy pancreases has been shown to be a potentially viable option to treat diabetes in humans, as long as rejection can be avoided.
The researchers’ current findings come on top of a previous study in which they grew rat pancreases in mice. Although the organs appeared functional, they were the size of a normal mouse pancreas rather than a larger rat pancreas. As a result, there were not enough functional islets in the smaller organs to successfully reverse diabetes in rats.
Because the transplanted islets contained some contaminating rat cells, the researchers treated each recipient mouse with immunosuppressive drugs for five days after transplant. After this time, however, the immunosuppression was stopped. After about 10 months, the researchers removed the islets from a subset of the mice for inspection.
‘We examined them closely for the presence of any rat cells, but we found that the mouse’s immune system had eliminated them. 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,’ said Nakauchi.
Importantly, the researchers also did not see any signs of tumour formation or other abnormalities caused by the pluripotent mouse stem cells that formed the islets. The researchers believe the lack of any signs of cancer is likely due to the fact that the mouse pluripotent stem cells were guided to generate a pancreas within the developing rat embryo, rather than coaxed to develop into islet cells in the laboratory.
Although the findings provide proof-of-principle for future work, much research remains to be done. Ethical considerations are also important when human stem cells are transplanted into animal embryos, the researchers acknowledged.
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