Oxygen Levels: Critical to the Development & Function of Insulin-Producing Cells
Background:
Insulin producing islet cells need a lot of oxygen to survive. In their native pancreas, islet cells make up only 1-2% of all cells, but they use up to 25% of the oxygen flowing through the organ.
DRI scientists have been investigating this critical role of oxygen and are studying ways to both mimic the oxygen-rich environment of the native pancreas, and more efficiently deliver oxygen to insulin-producing cells.
Research Focus:
One area of focus is the role oxygen plays in developing stem cells into insulin-producing cells. That transformation of stem cells, if successful, could provide an unlimited supply of islet cells for transplantation. But the success hinges on, among other things, providing those developing cells with the oxygen supply they need to grow.
When developing stem cells are cultured using traditional laboratory methods, the cells can suffocate from lack of oxygen. So researchers here at the DRI have created a new device that provides cells with an oxygen environment that’s more like their native pancreas.
We call it the “oxygen sandwich.” The device sandwiches developing stem cells between two oxygen sources; a top one that diffuses air through the culture medium, and a bottom one that diffuses air through a silicon membrane incorporating an oxygen binding substance.
The results demonstrate the critical need to provide developing islets with an adequate oxygen supply. Stem cells in the oxygen sandwich produced 100 times more insulin-producing cells compared to those in traditional plastic culture containers.
Beyond the oxygen sandwich, we’re researching other approaches to provide critically-needed oxygen to islet cells.
- We’ve developed synthetic tissue scaffolds that distribute islet cells evenly within a space so that oxygen and nutrients can reach each one.
- We’re planning to conduct clinical trials during which type 2 diabetes patients will undergo a series of treatments in a hyperbaric chamber. After breathing 100% oxygen during treatments, we’ll determine whether the combination of oxygen and stem cell infusion can help the pancreas to either recover or function well enough to allow patients to significantly decrease or stop their medications.
Leading to a Cure: How this Research Supports our Mission
Oxygen plays a critical role in the development and function of insulin-producing cells. If we can deliver oxygen more effectively to stem cells as they mature in the lab, we can create an unlimited supply of islet cells for transplantation. And if we can ensure that transplanted cells are distributed evenly throughout the transplant space, those cells will be better able to absorb the oxygen and nutrients they need to survive.
Mimicking the native environment of the pancreas, the oxygen sandwich provides the necessary oxygen for islets to develop and thrive.
Experiments compare traditional culture conditions (top photo) to new DRI technology (bottom) that delivers higher levels of oxygen to the tissues and cells – within normal range during pancreatic development.
The red color indicates the presence of insulin. The green identifies glucagon. Both are central for healthy islet cells.
As shown in the bottom photo, a substantial increase was seen in both insulin and glucagon production in the pancreatic cells cultured in the oxygen rich containers.
