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

1型糖尿病是一种患者体内很少或没有产生胰岛素的β细胞的疾病，这会导致高血糖水平。自从近一个世纪前胰岛素被发现以来，新的糖尿病病例出现了惊人的增长，但治疗1型糖尿病的唯一方法仍然是通过注射或泵送胰岛素。虽然胰岛素可以成功地控制糖尿病症状，但并发症的风险非常高，持续的血糖管理对患者的生活来说是一个真正的负担。通过替换失去的β细胞，再生医学为治愈糖尿病提供了新的希望。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效果都还在研究中。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iPSCs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从肿瘤蛋白（Matrigel）衍生的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的可变性，Matrigel与人类的任何翻译使用不兼容。我们已经开发出由化学家设计的专用凝胶（peg基水凝胶），同样可以为细胞提供3D支架，并提供安全的替代Matrigel。我们相信，确定允许胰腺祖细胞在这些水凝胶中扩张的条件，可以极大地提高β细胞用于人类治疗的安全性和功能。我们希望我们的发现为开发新的、更有效的策略来补充糖尿病患者失去的β细胞铺平道路，以实现糖尿病的最终治疗目标：“无糖尿病”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.