Development of non-invasive cell-based therapy for retinal degeneration and assoc

开发针对视网膜变性及其相关的非侵入性细胞疗法

基本信息

批准号：
8392291
负责人：
Shaomei Wang
金额：
$ 39.66万
依托单位：
CEDARS-SINAI MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-01-01 至 2015-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8392291
关键词：
Animal Model Area Autologous Back Blindness Blood Vessels Bone Marrow CXCR4 gene Cell Adhesion Molecules Cell Survival Cell Therapy Cells Cessation of life Clinic Clinical Clinical Trials Development Disease Dose Effectiveness Encapsulated Ethics Eye Genetic Growth Factor Homing Human Injection of therapeutic agent Intravenous Left Light Mediator of activation protein Medicine Mesenchymal Stem Cells Methods Modeling Modification Molecular Mus Mutation Nature Neurodegenerative Disorders Pathology Patients Photoreceptors Play Process Public Health Rattus Research Research Proposals Retina Retinal Retinal Degeneration Risk Rodent Model Role Route Running Safety Social Impacts Staging Stem cells Stromal Cell-Derived Factor 1 Structure Surgeon Testing Therapeutic Effect Time Translations Treatment Protocols Vision autocrine base chemokine college cytokine effective therapy experience gene therapy implantation intravenous administration intravenous injection intravitreal injection lens novel strategies paracrine photoreceptor degeneration protective effect regenerative repaired response stem cell biology stem cell therapy subretinal injection

项目摘要

Summary Retinal degeneration and related diseases are the leading cause of blindness and represent a major public health burden with economical and social impacts. As photoreceptor loss, the development of secondary vascular pathology causes disastrous consequences for vision. There is no effective treatment available. Our recent study revealed that a single intravenous injection of bone marrow derived mesenchymal stem cells (MSCs) at early stages of degeneration can preserve photoreceptors from death, sustain visual function, and limit pathological vascular changes in a rodent model of retinal degeneration. We propose to develop a treatment protocol that preserves vision and limits vascular pathology using non-invasive stem cell therapy in rodent models for retinal degeneration. We hypothesize that systemic administration of MSCs to treat ongoing retinal degeneration will slow the progress of photoreceptor loss and stabilize/repair the secondary vascular pathology by promoting the release of paracrine and autocrine mediators. The following specific aims are proposed: (1) Determine dose-response and long-term safety and efficacy of MSC treatment at early stages of degeneration in the RCS rat; (2) Investigate the neuro-vascular protective effects of MSCs at later stages of degeneration in the RCS rat and in Elovl4 mouse; (3) Examine the molecular mechanism of MSC homing to the retina and efficacy after intravenous administration. Based on the current extensive clinical experience using MSCs as therapy for both regenerative and degenerative medicine, if positive results are obtained in animal models, this treatment has a realistic likelihood of translation to the clinic.

概括视网膜变性和相关疾病是失明的主要原因，代表了主要公众健康负担具有经济和社会影响。作为感光器损失，次要的发展血管病理对视力造成灾难性后果。没有有效的治疗方法。我们的最近的研究表明，单次静脉注射骨髓衍生的间充质干细胞（MSC）在退化的早期阶段可以保留感光体免受死亡，维持视觉功能和在视网膜变性的啮齿动物模型中限制病理血管变化。我们建议开发一个治疗方案，可维护视力并限制使用非侵入性干细胞疗法的血管病理视网膜变性的啮齿动物模型。我们假设系统管理MSC以治疗正在进行的视网膜变性会减慢感光器损失的进展并稳定/修复次级血管通过促进旁分泌和自分泌介质的释放来病理学。以下具体目的是提议：（1）确定MSC治疗早期剂量和长期安全性和疗效 RCS大鼠的变性；（2）研究MSC在后期的神经血管保护作用 RCS大鼠和Elovl4小鼠的变性；（3）检查MSC归巢的分子机制静脉内给药后的视网膜和功效。根据当前的广泛临床经验使用MSC作为再生和退化性医学的治疗动物模型，这种治疗方法具有转化为诊所的现实可能性。