A potential solution for the chronic shortage of organs for transplant may have been found by researchers who successfully transplanted pancreatic cells from rats to mice, a study published this month in Nature revealed.
Researchers at the Stanford University School of Medicine and the Institute of Medical Science at the University of Tokyo successfully transplanted mouse pancreases grown in rats into mice with diabetes, reversing the disease.
The research findings suggest that similar techniques could be used to generate matched, transplantable human organs in large animals like pigs or sheep, the research team said, as well as save transplant patients from life-long reliance on immunosuppressant drugs.
The first step of the complex experiment involved implanting mouse stem cells into rat embryos that had been genetically engineered to be unable to develop a pancreas, and were thus forced to rely on the mouse cells to grow the organ.
Once the rats were born and grown, the researchers transplanted the insulin-producing pancreatic cells, which cluster together in groups called islets, from the rats into mice that were genetically matched to the original stem cells. The mice had been given a drug to cause 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, a 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.”
The current study was built on an earlier experiment in which the same research team grew rat pancreases in mice. Although that was successful, the new pancreases were only mouse-sized, and too small to provide enough cells to reverse the diabetes in rats. To solve the problem, the researchers swapped animals, choosing to grow the smaller mouse organ inside the rat.
The pancreases functioned normally in the rats, regulating their blood sugar, and because the rats were injected with the mouse stem cells at the embryonic stage, their bodies accepted the foreign cells and did not have an immune system response to them, the researchers said.
Most of these mouse-derived organs grew to the size expected for a rat pancreas, rendering enough individual islets for transplantation, the researchers explained.
Next, the researchers transplanted 100 islets from the rat-grown pancreases back into mice with diabetes. The mice that received the transplants developed normal blood sugar levels and maintained them for more than 370 days, the study results reported.
Because there were some “contaminating” rat cells mixed with the mouse pancreatic islets, the researchers gave the mice immunosuppressive drugs for five days after transplant, but then stopped it to see how the mice immune systems would respond.
After 10 months, the areas of transplanted cells were removed from the mice and examined.
“We examined them closely for the presence of any rat cells, but we found that the mouse’s immune system had eliminated them,” said Nakauchi. “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.”
The researchers also stressed that there were no signs of tumor formation or other abnormalities caused by the pluripotent mouse stem cells that formed the pancreatic cell islets, a common problem when using stem cells to grow new tissues or structures.
“We 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,” the researchers explained.
The researchers are now working on developing similar animal-to-animal experiments to generate kidney, liver, and lung tissue.
“Although the findings provide proof-of-principple 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 concluded.