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

糖尿病细胞替代疗法的新策略：USP7 在 iPSC 和成体类器官 β 细胞分化中的作用

• 批准号: MR/X01813X/1
• 负责人: Rocio Sancho
• 金额: $ 124.54万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX01813X%2F1
• 关键词: New; strategies; cell; replacement; therapies

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.

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，替代细胞的来源和它们的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，一种新的机制，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大大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。