A Study Using Human Stem Cells Ended Up Reversing Diabetes in Mice

By: April Carson



Results seen in a new study with mice might be successfully duplicated in people if a method for turning human stem cells into insulin-producing cells has great potential for future diabetes therapies.


In 2020, researchers discovered a new procedure to convert human pluripotent stem cells (hPSCs) into insulin-producing beta cells that was not previously known. When these insulin-producing cells were transplanted into mice with a type of diabetes that produces an acute form of the disease, their condition was cured within days.


"These mice had extremely severe diabetes, with blood sugar readings of more than 500 milligrams per deciliter of blood – levels that could be deadly to a person," said medical engineer Jeffrey R. Millman from Washington University in February 2020.


"When we injected the insulin-producing cells into the mice, their blood glucose levels recovered and stayed normal for many months.


Pluripotent stem cells are immature, undifferentiated cells with the potential to develop into various types of cells throughout the body. In the diabetic situation, understanding that potential entails researchers being able to modify stem cells into insulin-producing cells that diabetics lack, allowing them to manage high blood sugar and stay healthy.


For years, scientists have been attempting to accomplish this in animals, with some modest successes in animal models indicating that our understanding of the mechanisms involved is growing.


The Millman Lab, too, has been productive. They developed a technique for producing insulin-producing cells that responded to glucose in 2016. A few years later, they discovered how to boost the amount of insulin production in stem-cell-derived pancreatic beta cells.



In the most recent research, they addressed another problem: decreasing the amount of "off target" cells produced by these processes when blank cells become other types of unintended cells.


"When you're trying to turn a human stem cell into an insulin-producing beta cell, for example, or a neuron or a heart cell, you can end up creating other cells that you don't want," Millman added.


"In the case of beta cells, we may obtain different sorts of pancreas or liver cells.

Researchers at University of Edinburgh say that stem cell treatments usually mirror healthy cells, so the problem isn't with the good ones. The 'off target' cells aren't dangerous, but they aren't useful for things like glucose control, which limits the therapeutic impact of stem cell procedures when you're working with fewer practically relevant cells.


However, the newest approach appears to be able to keep cell differentiation on track.


Transcription factors that direct stem cells toward becoming pancreatic cells were connected to the cell's cytoskeleton, a support structure inside cells that serves as a sort of skeleton, made up of microfilaments of various protein fibers, in the 2020 study.


Actin is one of the proteins examined. It has an important function in cellular activity and, it turns out, cell differentiation as well.


"We learned that changing cell-material interactions and the state of the actin cytoskeleton altered the timing of endocrine transcription factor expression and pancreatic progenitors' capacity to differentiate into stem-cell-derived beta cells," according to the researchers.


In other words, we may more effectively regulate the actin cytoskeleton to ensure the production of insulin-producing cells, and that bodes well for stem cell therapies in the future if the mouse model is anything to go by.


"We were able to produce more beta cells and those cells functioned better in the mice, some of which survived for over a year," said Millman. "Control animals who did not receive the cell transplants died as a result of their diabetes."


That's not all, either. The scientists also discovered that the same cytoskeletal techniques could be used to better regulate the differentiation of other sorts of cells, such as liver, esophagus, stomach, and intestine cells. If this is true, then the procedure may be used to improve stem cell therapies for a variety of diseases.


Of course, we can't forget where we started: this therapy has only been tested in animals; as the researchers point out, we're a long way off being able to heal individuals with this type of experimental therapy.


However, while the study's findings are encouraging, they may point to a possible future in which we may accomplish exactly that.


The authors of the study, which was published in Molecular Cell, said that their work "highlights the synergistic action of cytoskeletal dynamics with soluble biochemicals to regulate endodermal cell fate," thus opening up new possibilities for improving differentiation outcomes.



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About the Blogger:


April Carson is the daughter of Billy Carson. She received her bachelor's degree in Social Sciences from Jacksonville University, where she was also on the Women's Basketball team. She now has a successful clothing company that specializes in organic baby clothes and other items. Take a look at their most popular fall fashions on bossbabymav.com


To read more of April's blogs, check out her website! She publishes new blogs on a daily basis, including the most helpful mommy advice and baby care tips! Follow on IG @bossbabymav


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