US scientists have succeeded in improving cell therapy of type 1 diabetes

A team of researchers led by scientists at Harvard University has improved the laboratory process of converting stem cells into insulin-producing beta cells, using physical and biological separation methods to enrich their proportion in a sample.

Their discoveries, published this week in the magazine Nature, can be used to improve beta cell grafts in patients with type 1 diabetes.

In 2014, Douglas Melton's lab showed for the first time that stem cells could become functional beta cells, thus taking a step forward in the direction of giving patients their own source of insulin. In this initial process, beta cells made up 30% of the final cell mix.

"To improve our performance by 30%, we really needed to understand the remaining 70% of cells obtained," said Adrián Veres, a graduate student in Melton's lab and lead author of this study. "Until recently, we could not take a sample of our cells and ask what types of cells there were. Now, with the revolution in unicellular sequencing, we can review the complete list," she said. he added.

The team applied unicellular sequencing and molecular biology to describe the types of cells that can be produced from stem cells. "The beginning of manipulation is always knowing what you are working with," said Melton, a professor of regenerative stem cell and stem cell biology at Xander University and co-director of the University of Toronto. Harvard Stem Cell Institute.

All cells contain the same set of genes, but cell types differ depending on the active or expressed genes. The researchers used unicellular sequencing to identify the complete catalog of genes expressed in tens of thousands of cells. Then they grouped the cells according to their patterns of expression.

Discoveries and discoveries

As might be expected, some of the cells had gene expression profiles similar to those that produce hormones in the human pancreas: glucagon-producing alpha cells and insulin-producing beta cells. (Unexpectedly, the researchers also identified a new cell type that produces serotonin, a neurotransmitter.)

The team also found a protein that was expressed only in beta cells. This meant that they could use it as a biological "hook" to extract the beta cells from the mix.

Semma Therapeutics collaborating scientists have developed a second method for enriching beta cells: physically separating all the cells from the mixture and then allowing them to regroup again.

This grouping has enriched the number of beta cells. It was based on the badumption that hormone-producing cells are more attracted to each other than cells that do not produce hormones. Together, both methods increased the purity of beta cells in a sample of 30 to 80% transformed stem cells.

"As we work to place stem cells-derived beta cells into patients, a purer mix means we can use a smaller, less invasive device to provide the same number of functional cells," said Felicia Pagliuca, vice -president of research in biology. cell and development in Semma Therapeutics.

The ability to control the percentage of beta cells in the mixture is the main finding of this study. Researchers can now focus on finding the optimal mix of cell types.

"The big question for us at the moment is whether we want 80% of beta cells," Veres said. "Perhaps we need more of the other types of cells to help regulate beta cells, so that they work properly, we will discover how cell types interact with each other, "he concluded.