Converting liver stem cells into insulin-producing cells

将肝脏干细胞转化为产生胰岛素的细胞

• 批准号: 6483934
• 负责人: Li Yin
• 金额: $ 9.95万
• 依托单位: IXION BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-15 至 2003-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6483934
• 关键词: biological signal transduction; cell differentiation; cell line; cell population study; gene expression; glucose; insulin; liver cells; pancreatic islets; phosphorylation; stem cells

Type 1 diabetes is caused by the progressive ablation of insulin- producing pancreatic beta cells by autoreactive T cells. The resulting insulin insufficiency often leads to uncontrolled glucose excursions despite regular insulin replacement therapy. Such hyperglycemic, over a long period of time, results in debilitating secondary complications However, glucose responsive insulin release achieved following whole pancreas and islet implantations is considered to be crucial to prevent the morbidity substantially based on the observations of Diabetes Control and Complications Trial that investigated the effect of intensive insulin regimen. Unfortunately, there is a severe shortage of pancreas for whole pancreas or islet implantations. This has become the basis for exploring tem cell based approach to generate islet/insulin-producing cells in vitro. Liver, with its enormous ability to regenerate, offers a promising source of sem cells that can be differentiated into insulin producing cells for implantation into insulin-dependent diabetics. While adult pancreatic stem cells remain uncharacterized and elusive, liver stem cells have been well characterized for their detection and purification. Our preliminary experiments with rat liver stem cell lines imply their potential for such differentiation. In this Phase I SBIR proposal, we will specifically characterize liver stem cells for the expression of genes related to pancreas/islet development and differentiation. Upon differentiation into insulin expression cells, we will study the glucose responsive insulin production kinetics and early signaling events such as phosphorylation Successful completion of this project will lead us to a more detailed Phase II grant that will explore in vivo functionality of liver stem cell derived islet producing cells in diabetic animal models. PROPOSED COMMERCIAL APPLICATIONS: This research project has the potential to produce glucose-responsive insulin-producing cells/islets for transplantation into insulin-dependent Type 1 & 2 diabetics from liver stem cells. Liver stem cells are easier to obtain and have been well characterized. Due to its immense regenerative capacity, liver remains to be a best source for autologous cell transplantation therapy of the future

1型糖尿病是由自动反应性T细胞的胰岛素产生胰岛β细胞的进行性消融引起的。尽管常规的胰岛素替代疗法，但最终导致的胰岛素功能不全通常会导致不受控制的葡萄糖游览。这种高血糖在很长一段时间内导致了衰弱的次要并发症，但是，在整个胰腺和胰岛植入后，葡萄糖反应式胰岛素释放释放到了至关重要的，认为这对于预防糖尿病控制的观察结果和复杂性试验的试验（研究强度胰岛素固定蛋白的作用）基本上是至关重要的。不幸的是，整个胰腺或小岛植入的胰腺严重短缺。这已成为探索基于TEM细胞的方法的基础，以便在体外生成胰岛/产生胰岛素的细胞。肝脏具有巨大的再生能力，提供了有希望的SEM细胞来源，可以将其分化为胰岛素产生细胞，以植入胰岛素依赖性糖尿病患者。虽然成年胰腺干细胞仍然没有表征且难以捉摸，但肝脏干细胞的检测和纯化已得到很好的特征。我们对大鼠肝干细胞系进行的初步实验暗示了它们进行这种分化的潜力。在此阶段I SBIR提案中，我们将特别表征肝干细胞的表达，以表达与胰腺/胰岛发育和分化有关的基因。分化为胰岛素表达细胞后，我们将研究葡萄糖反应性胰岛素生产动力学和早期信号事件，例如磷酸化成功完成该项目的完成，将使我们获得更详细的II期赠款，该赠款将探索糖尿病动物模型中肝脏干细胞衍生的小岛产生细胞的体内功能。拟议的商业应用：该研究项目有可能产生葡萄糖响应性的产生胰岛素的细胞/胰岛，以从肝脏干细胞中移植到胰岛素依赖性1和2型糖尿病患者中。肝干细胞更容易获得，并且已经表征了很好的表征。由于其巨大的再生能力，肝脏仍然是自体细胞移植疗法的最佳来源