Stem cells and regenerative medicine
Regenerative medicine is considered one of the most promising areas of medicine. It focuses on replacing or repairing cells, tissues, or organs that have been damaged or lost due to disease, injury, or aging. Researchers use pluripotent stem cells for this purpose. These unique cells naturally occur in early embryos. However, the use of embryonic pluripotent stem cells in the lab raises ethical concerns, limiting their widespread application.

This changed in 2006 with the discovery of induced pluripotent stem cells (hiPSCs). hiPSCs are created in the laboratory by ‘resetting’ adult cells, such as skin or blood cells, to a pluripotent state, allowing them to develop into many different cell types. hiPSCs can also multiply indefinitely in the lab, providing an almost unlimited source for producing new cells and tissues.

Towards new therapies to replace islets
Thanks to these unique properties, hiPSCs hold great potential for treating chronic diseases. Worldwide, researchers are working on methods to grow cells and tissues derived from hiPSCs for patient use. Françoise Carlotti, group leader at LUMC, explains: “In our lab, we focus specifically on developing safe and effective methods to produce islets from hiPSCs. Islets are clusters of cells found in the pancreas that contain insulin-producing beta cells. Beta cells are lost in type 1 diabetes due to an autoimmune reaction, making patients heavily reliant on insulin therapy to manually control blood sugar levels. Producing insulin-producing islets from hiPSCs — stem cell islets — could be a real game-changer, as it would provide an unlimited supply of cells to restore insulin production.”

To bring cell therapies to patients, they must meet very strict safety requirements, including high cell purity. During the lab cultivation process, other unwanted cell types may emerge, which could be harmful if transplanted.

Why make it complicated when it can be simple?
Carlotti and her team developed a straightforward method to improve the purity of stem cell islets. Researcher Bahareh Rajaei explains: “Cells have different densities due to variations in their content and structure. Pancreatic islets, for example, are denser than other cell types because they contain insulin-filled vesicles. Stem cell-derived islets can therefore be separated from unwanted cells by centrifuging them in a density gradient.” A density gradient is a liquid made of layers with different densities. Cells are added to the gradient, and during centrifugation, heavier cells move to the bottom while lighter cells remain at the top, allowing each layer to be collected separately. “This process not only improves the purity of the stem cell islets but also reduces the volume required to transplant sufficient islets, resulting in a safer final product,” says Rajaei.

This is the first time this method has been applied to stem cell-based products. While it was used to purify stem cell islets, it could also be applied to other cell types derived from stem cells, making it valuable for the entire field of regenerative medicine.

Future perspectives
To further streamline islet production, Carlotti and her team also optimized other parts of the protocol, such as how hiPSCs are cultured in the lab during their differentiation into insulin-producing islets.

Normally, hiPSCs are grown in plastic dishes in a single layer on the surface, limiting the number of cells produced. Carlotti explains: “We now produce stem cell islets in spinner flasks — culture flasks with a stirring mechanism. This allows the islets to grow while suspended in the culture medium, enabling the production of larger numbers of insulin-producing islets.”

Thanks to these improvements, LUMC researchers have taken an important step toward developing a new stem cell-based therapy for type 1 diabetes. Carlotti says: “There are high expectations for regenerative medicine, and we are excited to be part of this journey.”

Want to learn more?
The study has been published in Science Translational Medicine.

This research was made possible by the Diabetes Fund, the RegMedXB consortium, Stichting DON, the Bontius Foundation, and the Novo Nordisk Foundation Center for Stem Cell Medicine reNEW.