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

1型糖尿病是一种患者很少或没有产生胰岛素的β细胞的疾病，这导致高血糖水平。自从大约世纪前发现胰岛素以来，新发糖尿病病例出现了惊人的增长，但1型糖尿病的唯一治疗方法仍然是基于通过注射或泵输送胰岛素。虽然胰岛素给药可以成功地控制糖尿病症状，但并发症的风险非常高，并且所需的持续血糖管理可能是患者生活中的真实的负担。再生医学通过替代丢失的β细胞为糖尿病的治愈性治疗提供了新的希望。然而，替代细胞的来源、安全性、生产效率以及它们在体内的工作情况仍在调查中。在我们的实验室中，我们有令人兴奋的证据表明，能够从称为iPSC的特定干细胞产生β细胞的细胞池（胰腺祖细胞）可以在实验室中使用来自肿瘤蛋白（Matrigel）的3D支架进行扩增。使用这种方法可以产生无限量的β细胞。然而，由于安全性问题和批次间变异性，基质胶与人类的任何转化用途都不相容。我们开发了由化学家设计的专用凝胶（基于PEG的水凝胶），可以类似地为细胞提供3D支架，并提供Matrigel的安全替代品。我们认为，确定允许胰腺祖细胞在这些水凝胶中扩增的条件可以大大提高β细胞的安全性和功能性，以用于人类治疗。我们希望我们的研究结果为开发新的，更有效的策略来补充糖尿病患者丢失的β细胞铺平道路，以实现糖尿病的最终治疗目标：“无糖尿病”的生活。

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.