Over five years ago, Dr. Lawrence C.B. Chan and colleagues in his Baylor College of Medicine laboratory cured mice that had type 1 diabetes by using a gene to induce liver cells to make insulin.
“Now we know how it works,” said Chan, director of the federally designed Diabetes and Endocrinology Research Center at BCM and chief of the division of endocrinology in BCM’s department of medicine. “The answer is adult stem cells.”
There is a gene called neurogenin3 that proved critical to inducing cells in the liver to produce insulin on a continuing basis, said Chan and Dr. Vijay Yechoor, assistant professor of medicine-endocrinology and first author of the report that appears in the current issue of the journal Developmental Cell. The research team used a disarmed virus called a vector to deliver the gene to the livers of diabetic mice by a procedure commonly known as gene therapy.
“The mice responded within a week,” said Yechoor. The levels of sugar in their blood plummeted to normal and stayed that way for the rest of their normal lives.”
“This is a transient effect,” he said. “Liver cells lose the capacity to make insulin after about six weeks.”
However, they found that other cells that made larger quantities of insulin showed up later, clustered around the portal veins (blood vessels that carry blood from the intestines and abdominal organs to the liver).
“They look similar to normal pancreatic islet cells (that make insulin normally),” said Yechoor.
Chan warned that much more work is needed before similar results could be seen in humans. The gene therapy they undertook in the animals used a disarmed viral vector that could still have substantial toxic effects in humans.
“The concept is important because we can induce normal adult stem cells to acquire a new cell fate. It might even be applicable to regenerating other organs or tissues using a different gene from other types of adult stem cells,” he said.
Finding a way to use the treatment in human sounds easier than it is, he said. The environment in which cells grow appears to be an important part of the cell fate determination.
However, he and Yechoor plan to continue their work with the eventual goal of providing a workable treatment for people with diabetes.