Engineered Mini-Stomachs Could Be Future Of Diabetes Treatment
Published 1 Mar 2016
For decades, scientists have been trying to figure out how to replenish vital insulin-producing beta cells that are missing in type 1 diabetes, which affects an estimated 1.25 million children and adults in the United States. Indeed, major inroads have been made in engineering functional insulin cells in the lab that could be used as cell replacement therapies for treating diabetes. But one of the limitations of these experimental therapies is that, in type 1 diabetes, the body continues to inflict damage on native and transplanted insulin cells. So, some scientists believe a more desirable approach would involve a treatment in which beta cells could be produced in a renewable fashion to counteract their loss in the body.
Now, researchers may have found a way to replace these lost beta cells – by reprogramming stomach tissue. The researchers took samples of tissue from the lower stomach in mice and grew this tissue into mini-organs that, when transplanted back into animals, functioned as insulin-producing cells. While the research is still in early stages, the findings highlight the potential for development of engineered stomach tissue as a renewable source of functional beta cells to treat diabetes. The results appear in the journal Cell Stem Cell.
Located in the pancreas, beta cells store and release insulin, the hormone responsible for regulating glucose levels in the blood. In type 1 diabetes, the body’s own immune system mounts an attack against beta cells and destroys them. Without the ability to produce the amount of insulin the body needs, glucose builds up in the bloodstream. This rise in blood glucose levels leads to symptoms of type 1 diabetes.
In the study, senior author Qiao Zhou, of the Department of Stem Cell and Regenerative Biology at Harvard University, and his colleagues genetically engineered mice to express three genes that have the ability to convert other cell types into beta cells. This allowed the researchers to spot which cells in the body have the greatest insulin-producing potential. After flipping on these gene switches in the mice, the team observed that some of the cells in the lower stomach – a region called the pylorus, which connects the stomach to the small intestine – appeared to be most amenable to conversion to beta cells.
When the researchers tried reprogramming different cells in the mice to behave like beta cells, they found that cells in this area were most responsive to high glucose levels in the blood and were able to generate insulin to stabilize the blood sugar.
To test how effective these cells might be at churning out insulin, the researchers wiped out the pancreatic beta cells in one group of mice, which made their bodies completely dependent on the reprogrammed stomach cells for insulin. A group of control mice that did not undergo tissue reprogramming died within eight weeks. Meanwhile, the experimental mice’s reprogrammed cells maintained insulin production and were able to regulate glucose levels for up to six months – the amount of time the animals were tracked.
One feature that makes the pylorus advantageous to insulin production is that stem cells naturally replenish the gut tissue on a continuous basis. In the experimental mice, the stem cells in this lower stomach region were able to regenerate the insulin-producing cell population after the first set of reprogrammed cells were destroyed.
The findings were promising, but the team couldn’t transfer the same experiment to humans. To get closer to a clinical application, Zhou and his colleagues instead removed stomach tissue from mice and engineered it to express the same beta-cell reprogramming factors in the lab. They then coaxed the cells to grow into a tiny ball of tissues resembling a stomach. The researchers hoped the mini-organs would be able to produce insulin as well as refresh itself with stem cells. To test this, they implanted the mini-stomachs in the membrane that covers the inside of the mouse’s abdominal cavity and destroyed the mice’s pancreatic cells to see if the mini-organs would compensate.
Out of the 22 mice in the experimental group, five continued to have normal glucose levels after the transplant and destruction of pancreatic cells. While that number seems like a low success rate, it was what the team expected, and the results could pave the way for new models of therapies that could eventually replace missing beta cells in diabetic people.
“What is potentially really great about this approach is that one can biopsy from an individual person, grow the cells in vitro and reprogram them to beta cells, and then transplant them to create a patient-specific therapy,” Zhou said in a statement. “That’s what we’re working on now.”
Facebook
TwitterComments
You will also like
Diabetes: Discrimination, Professional Life, Plan Ahead... What do patients say?
9 Nov 2018 • 13 comments
Read the article
Read the article
