Recently, Mayo Clinic researchers have discovered how to manufacture cells capable of generating a hormone that regulates low blood sugar. In an interview with Omnia Health Magazine, Quinn Peterson, Ph.D., discusses how he and his team have developed a new method of mass-producing a cell product containing the hormone glucagon that is capable of protecting against hypoglycemia in animal models. Excerpts:
How does generating pancreatic cell types from renewable sources hold promise for cell replacement therapies for diabetes?
Diabetes is the result of damage or dysfunction of the cells of the pancreas that regulate blood glucose. Researchers (including those in our lab) have been working to develop methods to generate pancreatic cells that can be transplanted into patients and restore the ability to regulate blood glucose. One of those cell types, the pancreatic alpha cell is responsible for preventing low blood sugar. In patients with diabetes, these alpha cells often do not work adequately. In this study, we report a method to produce large quantities of these alpha cells and demonstrate that when transplanted into animals these cells are capable of preventing low blood sugar.
How does the hormone glucagon work?
One of the most acute dangers associated with diabetes is uncontrolled hypoglycemia or low blood sugar. If blood sugar levels fall too low, patients can experience coma or even death. The natural mechanism in the body to prevent low blood sugar is regulation by the hormone glucagon. It is secreted from alpha cells that signal the body to release glucose stores in response to hypoglycemia (low blood sugar). When blood sugars are low, alpha cells secrete glucagon into the bloodstream. The glucagon travels to the liver where glucose stores are released into the bloodstream in response to rising glucagon levels thus bringing blood glucose levels up to normal.
How successful were the trials on animals? Were there any important lessons learnt?
Animals that received transplanted alpha cells were protected from hypoglycemia and spent less time with low blood sugar levels than animals that did not receive the transplanted cells. These studies demonstrate the promise of these cells to prevent hypoglycemia.
What quality checks need to be met before mass manufacturing starts? When would the treatment become widely available?
Stringent quality, safety and manufacturing evaluations are required prior to clinical evaluation including stability, toxicity and long-term survival studies. In addition to these studies, testing in large animals is planned to evaluate the required dosing of the cell product. These studies will support the ultimate clinical evaluation of this therapy. Although this therapy is still under development, we aim to start these clinical studies by 2022 and if successful this treatment could be widely available to patients by the end of the decade.
What does the term “living medicine” mean?
The cell replacement therapy envisioned here represents a new way of thinking about medicine where treatment does not just impact the living organism, but the treatment itself is living—in this case, a living alpha cell. Transplanted alpha cells are not inert. They have the ability to sense conditions and adapt their response in reaction to changing condition in the patient. In this way, we think of this future therapy as a living medicine that functions autonomously to improve patient health.
This work was supported in part by benefactor gifts to the Mayo Clinic Center for Regenerative Medicine, which included the Khalifa Bin Zayed Al Nahyan Foundation.