Stem Cell Research May Lead to a Cure for Diabetes

A team of researchers working jointly at the University of Tokyo, University of Cambridge, King’s College (London), Stanford University, and the National Institute for Physiologic Sciences (Aichi, Japan) have successfully grown mouse pancreata inside the bodies of rats using transplanted mouse pluripotent stem cells (PSCs). Functional islet cells from the newly generated pancreata were then successfully transplanted into the bodies of diabetic mice. This groundbreaking study was published recently in Nature.

Pluripotent stem cells can develop into any type of cells or organs in the body. In this study, researchers injected PSCs from mice into rat embryos that had been genetically altered to develop without their own pancreata (a process referred to as interspecies blastocyst complementation). Once the rats developed pancreata, researchers isolated pancreatic islet cells from the rats and injected those cells into diabetic mice. The diabetic mice that received the transplanted islet cells became normoglycemic and remained so for over 370 days, the authors reported.

Organ rejection was a factor in the study, as some of the rats’ bodies rejected the mouse pancreata and some of the mice rejected the transplanted islet cells due to the unavoidable transplantation of some rat cells (eg, endothelial cells and stroma) along with the mouse cells. However, investigators reported that the transplant-recipient mice only required immunosuppressive medication for a short time (five days), and in most cases the immune systems of the mice simply eliminated the foreign rat cells.

Tumorigenesis is generally a concern when dealing with PSCs, due to their potential to become any cell type. However, the authors reported that this was not observed in the mice that received the transplanted islet cells, noting that “the blastocyst complementation system excludes the possibility of teratoma development through contamination with undifferentiated PSCs.”

Investigators are hopeful that their work may pave the way to finding a cure for diabetes, as the transplanted pancreata are fully functional. They report, “The pancreata generated through blastocyst complementation probably underwent near-normal differentiation with proper epigenetic changes, leading to generation of fully functional endocrine, as well as exocrine cells.”

The scientists also hope their research may lead to the successful transplantation of human organs grown within larger animals, such as pigs or sheep, and that this technology may someday provide alternate sources for organ transplants, reducing dependence on the use of donated human organs.

The fact that organ rejection was minimized in transplant-recipient mice seems encouraging, the authors say, as it suggests that the immune system of a human might be able to similarly eliminate a limited number of ovine or porcine cells with minimal requirements for immunosuppressive medication following a successful organ transplantation. Researchers acknowledge, however, that mice and rats are more genetically similar than humans and pigs, or humans and sheep.

These physiologic and genetic interspecies differences are among the many challenges scientists must overcome in order to advance this research. The authors further acknowledge the ethical concerns associated with injecting human PSCs into animal embryos, as some of the stem cells may develop into human cells or organs, including brain cells, or the germ cells from which human ova and sperm are derived.

These investigators are also working on similar methods for producing kidney, liver, and lung tissue for transplantation.

Dr. Todd-Jenkins received her VMD degree from the University of Pennsylvania School of Veterinary Medicine. She is a medical writer and has remained in clinical practice for over 20 years. She is a member of the American Medical Writers Association and One Health Initiative.