Scientists reverse diabetes in mice with lab-grown insulin cells

Type 1 diabetes develops when the immune system attacks and destroys the pancreas’s insulin-producing cells. Without insulin, the body cannot properly absorb glucose from the bloodstream, leading to dangerous blood sugar levels. Replacing these lost cells has long been seen as a promising solution, but earlier attempts to grow them from stem cells have produced inconsistent results.

“We have developed a method that reliably produces high-quality insulin-producing cells from multiple human stem cell lines. This opens up opportunities for future patient-specific cell therapies, which could reduce immune rejection,” says Per-Olof Berggren, professor at the Department of Molecular Medicine and Surgery, Karolinska Institutet, and corresponding author alongside Siqin Wu, researcher at Spiber Technologies AB (formerly at Karolinska Institutet).

More Mature and Functional Insulin Cells

The new approach improves how these cells are produced, resulting in insulin-producing cells that are both more refined and more functional than those made with earlier techniques. In laboratory experiments, the cells released insulin and showed a strong response to glucose levels.

When transplanted into diabetic mice, the cells gradually restored the animals’ ability to regulate blood sugar. The researchers placed the cells in the anterior chamber of the eye, allowing them to observe how the cells developed and functioned over time.

“This is a technique we use to monitor the development and function of the cells over time in a minimally invasive way,” explains Per-Olof Berggren. “We observed that the cells gradually matured after transplantation, retaining their ability to regulate blood sugar for several months, which demonstrates their potential for future treatments.”

Overcoming Long-Standing Challenges

Stem cell therapies for type 1 diabetes are already being tested in clinical trials, but they face several hurdles. One major issue has been that stem cells often turn into a mix of useful and unwanted cell types, which can increase risks. Another challenge is that lab-grown insulin cells are often not mature enough to respond effectively to glucose.

To address these problems, the researchers refined the culture process and allowed the cells to form natural three-dimensional clusters. This step reduced the number of unwanted cell types and improved how well the cells responded to glucose.

“This could solve several of the problems that have previously hindered the development of stem cell-based treatments for type 1 diabetes. Building on this, we will work towards clinical translation aiming at treating type 1 diabetes,” says Fredrik Lanner, professor at the Department of Clinical Science, Intervention and Technology, Karolinska Institutet, and last author of the paper.

Toward Future Diabetes Treatments

The study was a collaboration between Karolinska Institutet and KTH Royal Institute of Technology in Sweden. Funding came from several organizations, including the Swedish Research Council, STINT, the Knut and Alice Wallenberg Foundation, the Novo Nordisk Foundation, the European Research Council’s (ERC) Advanced Grant, the Erling-Persson Family Foundation, the Jonas & Christina af Jochnick Foundation, the Swedish Diabetes Association, Vinnova and Karolinska Institutet’s Strategic Research Program in Diabetes. Some researchers also report ties to companies, including patent applications and employment at Spiber Technologies AB and Biocrine AB (see publication for full details).