New strategies in cell replacement therapies for diabetes: role of USP7 in iPSC and adult organoids beta cell differentiation

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、生产效率以及它们在体内的工作效果都还在研究中。在我们的实验室里，我们有令人兴奋的证据证明了一种新机制，通过这种机制，参与β细胞分化的关键蛋白质Neurogenin 3可以变得更加稳定，从而增加其从不同细胞来源制造β细胞的潜力。我们相信，确定允许iPSC或成人胰腺细胞增强分化的条件可以极大地提高用于人类治疗的β细胞的产量和功能。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 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 of a novel mechanism by which the key protein involved in beta cell differentiation, Neurogenin 3 can be made more stable and therefore increase its potential to make beta cells from different cell sources. We believe that identifying the conditions that allow for the enhanced differentiation of iPSC or Adult pancreas cells could greatly improve the yield 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.