Development of platforms for sorting, production, editing of beta cells

开发用于分类、生产、编辑 β 细胞的平台

基本信息

批准号：
10682155
负责人：
Amit Choudhary
金额：
$ 69.15万
依托单位：
BROAD INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-05 至 2028-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10682155
关键词：
Affinity Anti-Inflammatory Agents Benchmarking Beta Cell Binding Biology CRISPR/Cas technology Cadaver Cell Culture Techniques Cell Line Cell Membrane Permeability Cell Proliferation Cell Survival Cell Transplantation Cell physiology Cell secretion Cells Chemicals Clinical Trials Dependence Development Dyes Encapsulated Endocrine Engineering Exhibits Face Fibrosis Foreign-Body Reaction Generations Genes Genetic Genome engineering Glucose Graft Rejection Harmine Human Immune Immune system Immunosuppressive Agents Impairment Insulin Insulin-Dependent Diabetes Mellitus Interleukin-10 Ions Islets of Langerhans Islets of Langerhans Transplantation Knock-in Legal patent Libraries Life Ligands Mitogens Pancreas Patients Plasma Population Prevention Procedures Prodrugs Production Proliferating Property Protein Tyrosine Kinase Protocols documentation Quality of life Replacement Therapy Reporting Scheme Sorting Source Specificity Surgical Replantation System Teratoma Therapeutic Therapeutic Effect Time Transplantation Treatment Cost Treatment Efficacy Undifferentiated United States National Institutes of Health Validation Zinc cell type chemical conjugate cost cost effective cytokine differentiation protocol elastase inhibitor embryonic stem cell engineered beta cell fluorophore genome editing glycemic control immunoregulation implantation in vivo induced pluripotent stem cell inhibitor islet large scale production mouse model precise genome editing side effect small molecule stem cells therapeutic development transplantation therapy

项目摘要

PROJECT SUMMARY Patients suffering from type 1 diabetes must undergo burdensome, often lifelong, exogenous insulin dependence. Up to now, the only available replacement therapy is to transplant islets from cadaveric donors. However, such procedures present hurdles such as the scarcity of available donors and the rejection of transplanted cells by the patient’s immune system. Also, over time, the transplanted islets tend to die. Several types of stem cells, including embryonic stem cell and induced pluripotent stem cell, have been extensively studied to generate glucose-responsive insulin-secreting cells and represents a more tenable source of islets. However, a significant concern for transplantation therapy is the need for immunosuppressive drugs, which exhibit long term side effects and hinders the feasibility of this approach to the large population of T1D patients. Furthermore, cost-effective and large-scale production of these stem cell-derived beta cells is still a major challenge. We propose to apply chemical biology and genome engineering approaches to develop platforms for efficient sorting, production, and editing of these beta cells. PHS 398/2590 (Rev. 06/09) 1 Continuation Format Page

项目概要患有 1 型糖尿病的患者必须接受繁重的、通常是终生的外源性胰岛素治疗到目前为止，唯一可用的替代疗法是移植尸体捐献者的胰岛。然而，此类程序存在一些障碍，例如可用捐赠者的稀缺以及捐赠者的拒绝此外，随着时间的推移，移植的胰岛细胞往往会死亡。干细胞的种类主要包括胚胎干细胞和诱导多能干细胞研究产生葡萄糖反应性胰岛素分泌细胞并代表更可靠的胰岛来源。然而，移植治疗的一个重要问题是需要免疫抑制药物，这表现出长期副作用并阻碍了这种方法对大量 T1D 患者的可行性。此外，具有成本效益的大规模生产这些干细胞衍生的β细胞仍然是一个主要的方法。我们建议应用化学生物学和基因组工程方法来开发平台。用于有效分类、生产和编辑这些 β 细胞。 PHS 398/2590（修订版 06/09）1 延续格式页