Recapitulating beta cell development adjacent to the islet vascular niche to advance beta cell replacement therapies for type 1 diabetes.

回顾胰岛血管生态位附近的 β 细胞发育，以推进 1 型糖尿病的 β 细胞替代疗法。

• 批准号: MR/X001261/1
• 负责人: Yasaman Aghazadeh
• 金额: $ 101.27万
• 依托单位: Queen Mary University of London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FX001261%2F1
• 关键词: Recapitulating; beta; cell; development; adjacent

Type 1 diabetes (T1D) is an autoimmune disease in which the immune cells destroy the beta cells located in the pancreatic islets of Langerhans. As the primary role of the beta cells is to produce insulin and lower blood sugar, people living with T1D lack sufficient insulin leading to high blood sugar levels, which puts them at increased risk of vascular, neuronal, kidney, and other diseases. The most common therapy for T1D is the administration of insulin through pumps or daily injections, which is burdensome as it is not a cure and could fail episodically. Transplantation of beta cells from organ donors offers long-term treatment for T1D, improves sugar control and quality of life in the majority of the recipients, and eliminates the need for insulin administration in certain patients. However, there is a shortage of organ donors; therefore, the scientific community aimed at developing alternative sources of beta cells for transplantation. To do so, human stem cells, which are cells with the potential to generate all human organs, have been guided towards pancreatic cell types such as the beta cells and are currently being assessed in clinical trials for safety and function. Reports from these trials indicated two major challenges: (i) poor survival after transplantation; (ii) insufficient insulin secretion in response to glucose. In this proposal, I have designed experiments that could address these two issues. My previous work demonstrated that connecting pancreatic cells to vessels allows the delivery of oxygen, nutrients, and signaling molecules required to survive, sense glucose and secrete insulin after transplantation into diabetic mice. Therefore, in this proposal, I aim to build on this study to generate vascularized beta cells to boost their function and simultaneously improve their survival post-transplantation.

1 型糖尿病 (T1D) 是一种自身免疫性疾病，其中免疫细胞破坏位于朗格汉斯胰岛的 β 细胞。由于β细胞的主要作用是产生胰岛素和降低血糖，1型糖尿病患者缺乏足够的胰岛素，导致血糖水平升高，从而增加他们患血管、神经、肾脏和其他疾病的风险。 T1D 最常见的治疗方法是通过胰岛素泵或每天注射胰岛素，但这种方法很麻烦，因为它不能治愈，而且可能会偶尔失败。器官捐献者的β细胞移植可以为T1D提供长期治疗，改善大多数接受者的血糖控制和生活质量，并消除某些患者注射胰岛素的需要。然而，器官捐献者短缺；因此，科学界致力于开发用于移植的β细胞的替代来源。为此，人类干细胞（具有生成所有人体器官的潜力的细胞）已被引导至β细胞等胰腺细胞类型，目前正在临床试验中评估其安全性和功能。这些试验的报告表明了两个主要挑战：（i）移植后存活率低； (ii) 对葡萄糖的反应胰岛素分泌不足。在这个提案中，我设计了可以解决这两个问题的实验。我之前的工作表明，将胰腺细胞与血管连接起来，可以输送糖尿病小鼠移植后存活、感知葡萄糖和分泌胰岛素所需的氧气、营养物质和信号分子。因此，在这项提案中，我的目标是在这项研究的基础上产生血管化的β细胞，以增强它们的功能，同时提高它们移植后的存活率。