Led by Goethe University (Frankfurt, Germany), a European team of researchers is working to develop a new method that could eliminate the need for people with type 1 diabetes to have lifelong insulin therapy.
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The research team plans to develop 3D cellular structures of insulin-producing cells (organoids) in the laboratory and work with pharmaceutical industry partners to develop a process for their mass production. The European Union is providing over 5 million Euros ($5.6 million) over the next four years to support the project, with the first clinical studies on transplantation of organoids planned after that.
Patients with type 1 diabetes are unable to produce insulin because of a genetic defect or an autoimmune disorder. They could be cured by transplanting a functional pancreas, but there are not nearly enough donor organs available. This is why researchers had the idea of growing intact insulin-producing cells from donor organs in the laboratory to form organoids, which they would then transplant into the pancreas of diabetes patients. The research tested their method in mice as a proof of concept, which was successful, according to Dr. Francesco Pampaloni, who coordinated the first project together with Prof. Ernst Stelzer at the Buchmann Institute for Molecular Life Sciences at Goethe University.
Researchers have only recently discovered how to produce organoids. Adult stem cells, which develop into cells for wound healing or tissue regeneration in the body, are the starting point. These cells can be grown in the laboratory through cell division and then allowed to differentiate into the desired cell type. The key is now to embed them in a matrix so that they grow into 3D structures. The organoids are typically spherical, hollow on the inside and have a diameter from approximately 20 µm to hundreds of micrometers. "If the structure were compact, then there would be a risk of the inner cells dying off after transplantation because they wouldn't be supplied by the host organ's cellular tissue," Pampaloni explains.
The research team is working to control the growth and differentiation of the filigree organoids under a microscope. To do so, they are using a light microscopy method developed by Stelzer that allows the growth of biological objects to be observed at the single-cell level in 3D. The project is called LSFM4Life because light-sheet fluorescence microscopy (LSFM) plays a key role in it.
The group is also developing quality assurance protocols because of the cooperation with industrial partners in Germany, France, the Netherlands, and Switzerland, with the original goal of the project being the large-scale production of organoids in accordance with good manufacturing practices for pharmaceuticals. Two research groups in Cambridge, England specialize in isolating insulin-producing cells from donor organs and growing organoids, while a group of clinicians in Milan, Italy is developing methods for transplanting organoids.
As is the case for all organ transplants, care will have to be taken with organoids as well so that rejection responses by the recipient's immune system are avoided. However, over time the researchers plan to build cell banks from which immunologically compatible cell types can be selected for every recipient.
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