26 February 2020

Improved methodology

Mice got rid of diabetes with the help of human stem cells

Polina Gershberg, Naked Science

Scientists from Washington University in St. Louis turned human stem cells into endocrine beta cells that produce insulin, and cured laboratory mice of diabetes with their help.

The researchers published an article about their work in Nature Biology (Hogrebe et al., Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells).

beta-cells.jpg

Clusters of beta cells under a microscope.

"These mice had very severe diabetes with sugar readings of more than 500 milligrams per deciliter of blood, which can be fatal for humans," study leader Jeffrey Millman says about the experiment. "When we injected the mice with insulin-secreting cells, within two weeks their blood glucose levels returned to normal and remained so for many months."

The method of converting stem cells into beta cells was developed by the same group of scientists two years ago. But then the researchers could not influence the condition of mice with diabetes. The fact is that when stem cells are forced to differentiate by a certain type, a mixture of target and non-target cells is obtained.

Non–target pancreatic cells did not damage anything when injected into the body of mice - but they also did not fight diabetes. "It takes about a billion beta cells to cure a person of diabetes. But if a quarter of them are actually liver cells or other types of pancreatic cells, <...> you will need 1.25 billion cells already. Coping with the disease will be 25% more difficult," Millman sums up.

Now researchers have managed to achieve a greater output of target cells in the process of differentiation – thanks to the discovered connection between the state of the cytoskeleton (the cell framework inside eukaryotic cells) and differentiation pathways. By inhibiting the polymerization of the actin protein in the cytoskeleton with the help of latrunculin A (an organic toxin of Red Sea sponges), scientists managed to direct differentiation along the desired "route".

The improved technique allowed Millman's team to obtain cell cultures that perform the task much better. The new method works effectively on stem cells from different sources, which significantly expands the possibilities of this technique in the study of various diseases and the development of methods for their treatment.

Scientists admit that their methodology still needs to be seriously improved so that it is suitable for the treatment of people suffering from diabetes. In particular, it is necessary to test the induced beta cells on larger animals and for long periods of time.

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