JDRF Research
Researchers Prompt Human Adult Liver Cells to Produce Insulin
Results of a recent study by JDRF-funded researchers in Israel offer patients new hope of regaining control of blood sugar levels by having their liver cells reprogrammed to secrete insulin.
Scientists at the Endocrine Institute in Tel Hashomer, Israel, stimulated human adult liver cells in a lab dish to produce insulin by giving them a gene that promotes insulin-secretion in pancreatic beta cells. The treated cells were then transplanted into diabetic mice, and over time were able to produce insulin and control blood glucose levels. To date, cell replacement therapies to reinstate insulin-producing tissue have been restricted by the shortage in tissue availability and by the need for lifelong immune suppression.
“This demonstrates proof-of-principle that some of the human body’s non-beta cells can be modified to secrete insulin in a glucose-responsive manner,” said JDRF Executive Vice President for Research Richard Insel, M.D. “Even partial success with this approach would provide an alternative source of cells for transplantation to reduce the amount of external insulin required by type 1 diabetes patients, significantly improving their quality of life.”
The research was led by Tamar Sapir, Ph.D., in the laboratory of Sarah Ferber, Ph.D., at the Endocrine Institute. The study was reported online May 16 by the Proceedings of the National Academy of Sciences.
The gene delivered to the liver cells, PDX-1, is active in the pancreas, which is an endocrine gland that also assists in digestion. The gene is also known to be critical for beta cell development. The researchers used a virus to ferry the PDX-1 gene into the cells, where it was incorporated into the cells’ DNA. The addition of PDX-1 to the liver cells caused them to take on characteristics of beta cells, enabling half the infected adult and fetal liver cells to store and secrete insulin.
When the genetically modified human liver cells were implanted into diabetic mice, they were relieved of the disease’s symptoms. The blood glucose levels in the mice significantly decreased and stayed lower for 60 days. When the scientists removed the human cells from some of the mice, the high glucose levels returned.
Two years ago, researchers at Tel Aviv University induced human fetal liver precursor cells to become insulin-secreting cells by delivering PDX-1. The new study is the first to use the PDX-1 method with adult human liver cells, which are much easier to obtain.
While results from the experiment are encouraging, it will likely be several years before the approach is tried in humans. “This is an exciting era in diabetes research, and progress is being made at an astonishing rate,” said Irene Cozar-Castellano, Ph.D. and Andrew F. Stewart, M.D., researchers at the University of Pittsburgh School of Medicine, in an accompanying commentary in the journal.