PEG-based hydrogels for iPSCs-derived regenerative therapies for diabetes

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Type 1 diabetes is a disease in which patients have very few or no insulin-producing beta cells, which results in high blood glucose levels. Since the discovery of insulin almost a century ago, there has been an alarming increase in new diabetes cases, but the only treatment for Type 1 diabetes is still based on delivering insulin via injections or pumps. While insulin administration can successfully control diabetic symptoms, the risk of complications is very high, and the continual blood sugar management required can be a real burden in patients' lives. Regenerative medicine offers new hope of a curative treatment for diabetes by replacing lost beta cells. However, the source of replacement cells, the safety, and the efficiency with which they can be produced and how well they work in the body are all still under investigation. In our lab, we have exciting evidence that the pool of cells (pancreatic progenitors) able to generate beta cells from specific stem cells called iPSCs can be expanded in the lab using a 3D scaffold derived from tumour proteins (Matrigel). Using this approach an unlimited amount of beta cells can be generated. However, Matrigel is incompatible with any translational use in humans due to safety concerns and batch-to-batch variability. We have developed specialised gels designed by chemists (PEG-based hydrogels) that can similarly provide a 3D scaffold for cells and provides a safe alternative to Matrigel. We believe that identifying the conditions that allow for the expansion of pancreas progenitors within these hydrogels could greatly improve the safety and functionality of beta cells to be translated for human therapy. We hope that our findings pave the way for the development of new, more efficient strategies to replenish lost beta cells in diabetes patients, in order to achieve the ultimate therapy goal for diabetes: a "diabetes free" life.