Synthetic substrates for the expansion and differentiation of hPSC-derived NPCs

用于 hPSC 衍生的 NPC 扩增和分化的合成底物

• 批准号: 9181880
• 负责人: DAVID A BRAFMAN
• 金额: $ 23.6万
• 依托单位: ARIZONA STATE UNIVERSITY-TEMPE CAMPUS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9181880
• 关键词: Address; Alzheimer' s Disease; Amyotrophic Lateral Sclerosis; Animal Disease Models; Astrocytes; Biochemical Genetics; Bioreactors; Cell Line; Cell Proliferation; Cell Therapy; Cells; Chemicals; Chromosomal Stability; Development; Differentiation and Growth; Disease; Disease model; Electrophysiology (science); Engineering; Etiology; Extracellular Matrix; Glass; Goals; Growth; Health Care Costs; Heterogeneity; Human; Huntington Disease; In Vitro; Lead; Libraries; Life; Methods; Modeling; Morbidity - disease rate; Neuraxis; Neurodegenerative Disorders; Neuronal Differentiation; Neurons; Neurotransmitters; Oligodendroglia; Parkinson Disease; Pluripotent Stem Cells; Polymers; Population; Preclinical Drug Evaluation; Proliferating; Property; Public Health; Recombinants; Regenerative Medicine; Replacement Therapy; Research; Slide; Societies; Source; Spinal Muscular Atrophy; Stem cells; Supporting Cell; Suspension Culture; System; Technology; Therapeutic; United States; Variant; base; cell growth; cell type; chemical property; clinical application; design; effective therapy; functional group; high throughput technology; human disease; human embryonic stem cell; induced pluripotent stem cell; interest; mortality; multipotent cell; nerve stem cell; nervous system disorder; neuron loss; new therapeutic target; novel; physical property; relating to nervous system; scale up; symptom treatment; tool

PROJECT SUMMARY ABSTRACT Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged neurons or supporting neural cells are of great therapeutic interest. Human neural progenitor cells (hNPCs) derived from human pluripotent stem cells (hPSCs, including human embryonic stem cells [hESCs] and human induced pluripotent stem cells [hiPSCs]) can proliferate extensively and differentiate into all the neural lineages (i.e. neurons, astrocytes, and oligodendrocytes) that compromise the central nervous system (CNS). Therefore, hNPCs and their differentiated progeny could provide the cellular raw material to model or treat a variety of nervous system disorders. However, the clinical application of these cells will require (i) defined, xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug screening purposes. To that end, we will use a novel high-throughput approach to systematically screen a rationally designed library of physicochemically-defined polymers to identify candidate synthetic substrates for the expansion and neuronal differentiation of hNPCs. Next, we will use these synthetic substrates as the basis for the engineering of low shear bioreactor-based systems for large-scale hNPC expansion and neuronal differentiation. The scaled-up cell populations will be assessed for their heterogeneity as well as their cellular, biochemical, genetic, and electrophysiological properties. The successful completion of this research will significantly advance the clinical application of hNPCs and their derivatives as it will enable the large-scale expansion and neuronal differentiation of hNPCs in quantities necessary for disease modeling, drug screening, and regenerative medicine applications.

项目摘要