According to a new study presented in the journal Cell Stem Cell, the key to a new cellular treatment for diabetes may lie in the stomach. Investigators have utilized stomach cells to develop “mini-organs” that deliver insulin when transplanted into mice.
In an effort to discover a cure for diabetes, investigators have invested years searching for approaches to replace these insulin-producing beta cells.
This recent research indicates that cells from the lower section of the stomach, well-known as the pylorus region, demonstrate the greatest possibilities to be reprogrammed to act like beta cells.
Reprogrammed stomach cells stabilized glucose levels in mice
Senior study author Qiao Zhou and colleagues genetically engineered mice to express 3 genes that have the capability to turn cells into beta cells.
This allowed the research team to determine which cells in the mice were most probably to have insulin-producing potential.
Commenting on their research senior author Qiao Zhou said;
We looked everywhere, from the nose to the tail of the mouse. We identified, interestingly, that some of the cells in the pylorus region of the stomach are most amenable to conversion to beta cells. This tissue seems to be the very best starting material.”
The pylorus area is the region that connects the stomach to the small intestine.
The investigators describe that when they reprogrammed different cells to act like beta cells, the pylorus cells had the best response to high blood glucose levels in the mice, generating insulin to be able to bring their glucose levels back to normal.
To examine the effectiveness of these cells, the investigators damaged the beta cells of 2 groups of diabetes mouse models. One group had their pylorus cells reprogrammed to behave like beta cells, while a control group did not go through pylorus cell reprogramming.
While the mice in the control group died within 8 weeks, those that had their pylorus cells reprogrammed managed their insulin and glucose levels for the whole monitoring period, which was around 6 months. This indicates that the reprogrammed pylorus cells compensated for the lack of beta cells.
Why pylorus cells seem to be the best cells to convert for insulin production?
Answering to above question Zhou said,
“From our molecular and physiological research, pylorus produced beta-cells seem to most closely mimic native beta cells in the pancreas and for that reason can do a superior work at regulating blood glucose.”
The research team notices that there is one more advantage to using cells from the pylorus region: stem cells in this region renew on their own consistently. They describe that when the initial set of reprogrammed cells were damaged in the mice, pylorus stem cells regenerated them.
“In different disease states, you have a continuous loss of beta cells,” claims Zhou. “We offer, in principle, an advantage to rejuvenate those.”
Mini-stomachs compensated for lack of beta cells
Zhou describes that in the research, mice were engineered to express 3 genes that have the capability to reprogram cells to beta cells, but this procedure would not be possible in humans.
To be able to address this issue and pave the way for a possible clinical therapy, the investigators produced some stomach tissue from mice and engineered the tissue cells in a laboratory to show aspects that would result in the conversion of stomach cells to beta cells.
Next, the team coaxed the reprogrammed cells to form a mini stomach measuring about 0.5-1 cm in diameter, prior to transplanting these small organs in the membranes of the abdominal cavities of the mice.
The investigators then damaged the beta cells of the mice to be able to see whether the mini-stomach would take over their job.
They identified that for 5 of the 22 mice who were transplanted with the mini stomachs, their blood glucose levels stayed normal. The team states that this is the success rate they anticipated to see.
Concluding this Zhou said,
When you put this jointly, you are simply asking the harvested stem cells to self-organize into an organ in a matrix. The restriction is all about whether the tissue you transplanted can effectively reorganize with the appropriate layers.”