Adult Stem Cells for Therapy of Visual Disorders

成体干细胞治疗视觉障碍

基本信息

批准号：
7429654
负责人：
MARTIN FRIEDLANDER
金额：
$ 334.65万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-06-01 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7429654
关键词：
Adenoviruses Adult Adverse effects Animal Model Area Astrocytes Attention Autologous Automobile Driving Back Basic Science Biochemical Genetics Biology Biomedical Engineering Biotechnology Blindness Blood Cells Blood Vessels Bone Marrow Bone Marrow Stem Cell Bone Marrow Transplantation Cataloging Catalogs Cell Fraction Cell Lineage Cell Therapy Cells Cellular biology Clinic Clinical Clinical Sciences Clinical Trials Coagulation Process Complement Complex Condition Data Degenerative Disorder Dependency Developed Countries Development Diabetes Mellitus Diabetic Retinopathy Disease Drug Kinetics Elements Embryo Emerging Technologies Endopeptidases Endothelial Cells Engineering Exhibits Eye Face Faculty Funding Genetic Transcription Genetic Vectors Genomics Gliosis Goals Guidelines Hematopoietic stem cells Histocompatibility Testing Human Human Resources Hypoxia Imagination Indium Individual Inherited Injection of therapeutic agent Injury Institutes Institution Integrins Interdisciplinary Study Ischemia Laboratories Lasers Lead Left Lentivirus Vector Life Longevity Macular degeneration Maintenance Manuscripts Mass Spectrum Analysis Mediating Metabolic Methods Modality Modeling Modification Molecular Molecular Profiling Monoclonal Antibody R24 Mus Myelogenous Myeloid Cells Myeloid Progenitor Cells Neonatal Nerve Degeneration Neurons Ophthalmologist Organ Oxygen Pathologic Processes Patients Peptide Hydrolases Photoreceptors Population Preparation Prevalence Principal Investigator Process Property Proteinase-Activated Receptors Proteomics Protocols documentation Publications Publishing Qualifying Receptor Signaling Recombinant Proteins Recombinants Research Research Personnel Research Project Grants Research Proposals Resources Retina Retinal Retinal Cone Retinal Degeneration Retinal Diseases Retinitis Pigmentosa Role Schedule Science Site Stem cells Stress Structure Surface System Techniques Telephone Testing Therapeutic Therapeutic Agents Therapeutic Studies Thinking Time Tissues Transcriptional Regulation Transfection Translating Translational Research Translations Tumor-Associated Vasculature Umbilical Cord Blood United States Vascular Diseases Vascular Endothelial Cell Viral Viral Vector Vision Disorders Visual Visual impairment Visual system structure Work adult stem cell angiogenesis base cell type cellular imaging cellular transduction clinical application concept erucylphosphocholine experience gene therapy interest killings lectures loss of function mouse model multidisciplinary neovascularization neuron loss neurotrophic factor novel novel therapeutics ocular angiogenesis pre-clinical prevent progenitor programs reconstruction relating to nervous system repaired retinal angiogenesis retinal neuron self-renewal stem stem cell therapy therapeutic angiogenesis tool vector

项目摘要

DESCRIPTION (provided by applicant): Nothing more dramatically captures the imagination of the visually impaired patient or the ophthalmologist treating them than the possibility of rebuilding a damaged retina with "stem cells." Defined as pluripotent cells capable of differentiating into a variety of cell types, stem cells can be derived from early embryos or adults and, under appropriate conditions, will differentiate into a variety of tissues. Stem cells have been identified in cord blood and adult bone marrow and represent a pool of progenitor cells that may serve to provide cells that maintain various tissue types as well as rescue/repair damaged tissue following injury or stress. These adult stem cells may have wide utility in the treatment of retinal vascular diseases and even inherited retinal degenerations. While the use of these cells to target neovasculature and contribute to the stabilization of otherwise friable vessels in ischemic retinopathies may seem intuitive, an associated neurotrophic effect observed recently (Otani, et al, 2004) is surprising but reasonable given newly emerging paradigms describing the existence of trophic "cross-talk" between local vascular networks and the tissues they supply. Thus, potential applications of these cells includes not only cell based therapeutic delivery of various trophic and static substances, but also as stabilizing elements in an otherwise unstable neovasculature of the type observed in ischemic retinopathies. In this proposal we will apply emerging technologies in stem cell biology, gene therapy, proteomics, large scale genomic analysis and live cell imaging to develop stem cell-based therapies for the treatment of vascular and degenerative diseases of the retina. This will be accomplished by (1) identifying and isolating a fraction of progenitor cells from adult bone marrow and cord blood that will target diseased vasculature in the retina and exert trophic rescue effects in animal models of retinal vascular and degenerative disease; (2) determining the mechanism whereby these trophic effects are achieved; (3) engineering a process for the preparation and characterization of the functional cell fraction; and (4) conducting the necessary pre-clinical pharmacological, toxicological and pharmacokinetic studies to take this approach into the clinics. If successful, these studies will lead to a novel therapeutic paradigm for currently untreatable vascular and degenerative diseases of the retina.

描述（由申请人提供）：没有什么比用“干细胞”重建受损视网膜的可能性更能激发视障患者或治疗他们的眼科医生的想象力了。干细胞被定义为能够分化成多种细胞类型的多能细胞，可以源自早期胚胎或成体，在适当的条件下，将分化成多种组织。干细胞已在脐带血和成人骨髓中被发现，代表着一组祖细胞，可提供维持各种组织类型以及在受伤或压力后拯救/修复受损组织的细胞。这些成体干细胞可能在治疗视网膜血管疾病甚至遗传性视网膜变性方面具有广泛的用途。虽然使用这些细胞来靶向新生血管并有助于稳定缺血性视网膜病中原本脆弱的血管似乎是直观的，但最近观察到的相关神经营养效应（Otani等，2004）令人惊讶，但考虑到描述存在的新出现的范式，这是合理的局部血管网络和组织之间的营养“串扰” 他们提供的纸巾。因此，这些细胞的潜在应用不仅包括基于细胞的各种营养物质和静态物质的治疗性递送，而且还包括作为缺血性视网膜病中观察到的不稳定新血管系统中的稳定元件。在这项提案中，我们将应用干细胞生物学、基因治疗、蛋白质组学、大规模基因组分析和活细胞成像领域的新兴技术，开发基于干细胞的疗法，用于治疗血管和视网膜退行性疾病。这将通过以下方式实现：（1）从成人骨髓和脐带血中鉴定并分离出一小部分祖细胞，这些祖细胞将靶向视网膜中患病的脉管系统，并在视网膜血管和退行性疾病的动物模型中发挥营养拯救作用； (2) 确定实现这些营养作用的机制； (3) 设计功能细胞组分的制备和表征工艺； (4) 进行必要的临床前药理学、毒理学和药代动力学研究，以将该方法应用于临床。如果成功，这些研究将为目前无法治疗的血管和视网膜退行性疾病带来新的治疗范例。