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Possible Diabetes Cure Coming Closer 

Apr 4, 2020
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Editor: David L. Joffe, BSPharm, CDE, FACA

Author: Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy 

Researchers successfully converted human cells to produce insulin, which reduced the blood sugar of mice dramatically after being infused — an early step towards a potential diabetes cure. 

Principal investigator Dr. Jeffrey R. Millman, an assistant professor of medicine and biomedical engineering at Washington University, revealed the vital breakthrough on February 24th that they successfully cured diabetes in mice by infusing them with converted human cells which were programmed to produce insulin.  

 

Converted human stem cells functionally cured the mice with diabetes for at least nine months and, in some cases for a whole year. The transformed cells produced insulin which allowed the mice to decrease their high blood sugars. For some mice, their blood sugars returned to normal after as little as two weeks. 

This breakthrough is significant, as over 400 million patients worldwide have diabetes, which is currently managed through diet, lifestyle changes, and medication.  

The outcomes of the research were published in the Nature Biotechnology journal. The researchers at Washington University converted human stem cells into pancreatic beta-cells to produce insulin and subsequently decrease blood sugar. “These mice had very severe diabetes with blood sugar readings of more than 500 milligrams per deciliter of blood — levels that could be fatal for a person — and when given the insulin-secreting cells, within two weeks their blood glucose levels had returned to normal and stayed that way for many months,” said principal investigator Dr. Jeffrey R. Millman. 

This research has been conducted before, albeit a little unsuccessfully. Researchers had initially discovered how to convert the cells to beta-cells. However, after the conversion, around 25% of cells were still not insulin–producing beta-cells but beta-cells of another kind such as liver cells.  

Millman explained that “a common problem when you’re trying to transform a human stem cell into an insulin-producing beta-cell — or a neuron or a heart cell —is that you also produce other cells that you don’t want. In the case of beta-cells, we might get other types of pancreas cells or liver cells. The more off-target cells you get, the less therapeutically relevant cells you have. You need about a billion beta-cells to cure a person of diabetes. But if a quarter of the cells you make are liver cells or other pancreas cells, instead of needing a billion cells, you’ll need 1.25 billion cells. It makes curing the disease 25% more difficult.”  

These non-insulin producing cells were not harmful to the mice. Still, they ultimately did not affect lowering blood sugar or improving the diabetic status and thus, the overall process remained futile. 

Therefore, the researchers resumed their exploration of cell conversion. They examined the cytoskeleton of the cell, sometimes referred to as the scaffolding of the cell, which allows the cell to interact with the surrounding environment. This physical interaction between the cell and its environment triggers a biochemical response; for example, a pancreatic beta-cell will produce insulin when it interacts with blood sugar. 

Millman added that “it’s a completely different approach, fundamentally different in the way we go about it. Previously, we would identify various proteins and factors and sprinkle them on the cells to see what would happen. As we have better understood the signals, we’ve been able to make that process less random. We were able to make more beta-cells, and those cells functioned better in the mice, some of which remained cured for more than a year.” This level of control over the resultant cell type is a huge advantage in allowing researchers to test this possible cure for diabetes further. 

Another substantial discovery during the research was that the cells used for conversion could originate from different sources, which consequently opens up the applicability of the technique. 

As mentioned, though there have been significant advances in this technology and methodology to program cells, we are still a long way away from human trials. Extensive tests still have to be completed to approve the safety and efficacy of the treatment. The next step in the research of a possible cure for diabetes using converted human stem cells is to test these cells on larger animals and for a more extended period to ascertain any long-term disadvantages.  

This recent breakthrough in a possible cure for diabetes is very promising for patients who have diabetes. The significance is not paltry since this is the first time a mammal (the mouse) has been functionally cured of diabetes, a disease formerly thought to be incurable. 

Practice Pearls: 

  • Human stem cells can be reliably converted into insulin-producing beta–cells 
  • Mice with diabetes treated with these transformed cells were functionally cured of diabetes for nine months, and some up to a year 
  • The initial findings were promising for future human trials 

Mulraney, Frances. “St Louis Scientists Cure Diabetes in Mice in Just Two Weeks Using Converted Human Cells.” Daily Mail Online, Associated Newspapers, 29 Feb. 2020, 

 

Mit Suthar, PharmD. Candidate, LECOM School of Pharmacy