Retinal Scaffolds: Synaptic and Stem Cell Integration

视网膜支架：突触和干细胞整合

• 批准号: 7938750
• 负责人: Jeffrey L Goldberg
• 金额: $ 38.04万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7938750
• 关键词: 3-Dimensional; Address; Age related macular degeneration; Amacrine Cells; Animals; Area; Astrocytes; Biocompatible Materials; Biological; Biological Assay; Biological Models; Brain; Calcium; Cell Communication; Cells; Development; Disease; Environment; Eye; Ganglion Cell Layer; Genes; Glaucoma; Goals; Image; In Vitro; Individual; Injury; Learning; Modeling; Monitor; Natural regeneration; Nervous system structure; Neural Retina; Neurons; Organ; Photoreceptors; Play; Preclinical Drug Evaluation; Process; Proliferating; Proteins; Regenerative Medicine; Replacement Therapy; Retina; Retinal; Retinal Degeneration; Retinal Ganglion Cells; Role; Screening procedure; Seeds; Specificity; Stem cells; Structure of retinal pigment epithelium; Study models; Synapses; System; Therapeutic; Thinking; Time; Tissue Engineering; Tissue Model; Tissues; animal tissue; cell type; cellular development; cost; experience; frontier; in vivo; interest; migration; neural circuit; neurodevelopment; neurotransmission; programs; public health relevance; relating to nervous system; response; retinal progenitor cell; scaffold; synaptogenesis; two-dimensional; 3-Dimensional; Address; Age related macular degeneration; Amacrine Cells; Animals; Area; Astrocytes; Biocompatible Materials; Biological; Biological Assay; Biological Models; Brain; Calcium; Cell Communication; Cells; Development; Disease; Environment; Eye; Ganglion Cell Layer; Genes; Glaucoma; Goals; Image; In Vitro; Individual; Injury; Learning; Modeling; Monitor; Natural regeneration; Nervous system structure; Neural Retina; Neurons; Organ; Photoreceptors; Play; Preclinical Drug Evaluation; Process; Proliferating; Proteins; Regenerative Medicine; Replacement Therapy; Retina; Retinal; Retinal Degeneration; Retinal Ganglion Cells; Role; Screening procedure; Seeds; Specificity; Stem cells; Structure of retinal pigment epithelium; Study models; Synapses; System; Therapeutic; Thinking; Time; Tissue Engineering; Tissue Model; Tissues; animal tissue; cell type; cellular development; cost; experience; frontier; in vivo; interest; migration; neural circuit; neurodevelopment; neurotransmission; programs; public health relevance; relating to nervous system; response; retinal progenitor cell; scaffold; synaptogenesis; two-dimensional

DESCRIPTION (provided by applicant): There is no 3-dimensional model for studying neural tissues, outside of explanting whole tissues from animals. For example, in the retina, degenerations of retinal ganglion cells (RGCs) in diseases like glaucoma or of photoreceptors and retinal pigment epithelium in diseases like age-related macular degeneration have generated considerable interest understanding the integration of stem cells or stem cell-derived neurons into neural tissues. But study of cell replacement therapies for such diseases outside of the whole animal has focused on a limited group of experimental approaches, either examining the explanted whole retina in culture, or studying the individual cell types in 2-dimensional cultures. Missing is any opportunity to learn about cellular development or integration in the 3-dimensional (3D) environment these cells normally experience. In addition, there are no 3-dimensional organ replacement therapeutic approaches for neural tissue. Here we will reverse this paradigm and create a new model system that combines in vitro advantages of experimental control and screening capability with in vivo advantages of studying neurons in their 3D environment, building towards organ replacement therapies for the nervous system. We will re-create the retina from its basic cell types in culture using 3D biodegradable scaffolds to provide a critical new model system to study how the retina develops, functions, and operates in response to disease or injury, and to study how stem cell-derived neurons synaptically integrate with their neighbors. Specifically, we will create 3D tissue models of the neural retina with retinal ganglion cells and amacrine cells, characterize and optimize their synaptic connectivity, and examine the ability of retinal progenitor cells added to these 3D tissue models to proliferate, differentiate, and integrate synaptically. Our goal is to develop 3D neural tissues for studying neural development, and ultimately for tissue replacement therapies. PUBLIC HEALTH RELEVANCE: Here we will create for the first time a three-dimensional neural tissue, the retina, ex vivo. This will allow for a new way to study stem cell integration into neural tissues and, as importantly, will build towards tissue replacement therapies for the nervous system.

描述（由申请人提供）：没有三维模型来研究神经组织，除了来自动物的整体组织之外。例如，在视网膜中，视网膜神经节细胞（RGC）在青光眼或光感受器等疾病中的退化（RGC）以及诸如年龄相关的黄斑变性等疾病中的视网膜色素上皮，了解了与干细胞或干细胞神经元进入神经细胞组织的整合。但是，对整个动物之外的此类疾病的细胞替代疗法的研究集中在有限的实验方法上，可以检查培养中的整个视网膜的植入植物，或者研究二维培养物中的单个细胞类型。缺少的是在3维（3D）环境中学习细胞发育或整合的任何机会。此外，没有针对神经组织的三维器官替代治疗方法。在这里，我们将扭转这种范式，并创建一个新的模型系统，该系统将实验控制和筛选能力的体外优势与在其3D环境中研究神经元的体内优势相结合，从而朝着神经系统的器官替代疗法建立了。我们将使用3D生物降解的脚手架从其培养物中的基本细胞类型中重新创建视网膜，以提供关键的新模型系统，以研究视网膜如何发展，功能和操作以响应疾病或损伤，并研究干细胞衍生的神经元如何与邻居融合。具体而言，我们将创建具有视网膜神经节细胞和无长熟细胞的神经视网膜的3D组织模型，对其突触连通性进行表征和优化，并检查视网膜祖细胞添加到这些3D组织模型中添加到这些3D组织模型中的能力，以增殖，区分和集成于突触。我们的目标是开发用于研究神经发育的3D神经组织，最终用于组织替代疗法。 公共卫生相关性：在这里，我们将首次创建三维神经组织，即视网膜，Ex Vivo。这将允许一种研究干细胞整合到神经组织中的新方法，并且重要的是，将朝着神经系统的组织替代疗法构建。