Enhancing photoreceptor integration using microglia-derived secreted factors

使用小胶质细胞衍生的分泌因子增强光感受器整合

• 批准号: 9903319
• 负责人: Deepak Ashok Lamba
• 金额: $ 40.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9903319
• 关键词: Accounting; Acute; Affect; Apoptosis; Astrocytes; Blindness; Cell Death; Cell Transplantation; Cells; Clinic; Clinical Trials; Cytoprotection; Data; Degenerative Disorder; Development; Direct Costs; Disease; Disease Progression; Dopamine; Dopaminergic Cell; Drosophila genus; Environment; Financial Hardship; Goals; Hemocytes; Homologous Gene; Immune; Immunologic Tests; Inherited; Injections; Light; Mammals; Microglia; Modeling; Morphology; Mus; Natural regeneration; Nervous system structure; Neurons; Parkinson Disease; Patients; Phenotype; Photoreceptors; Platelet-Derived Growth Factor; Pluripotent Stem Cells; Process; Protocols documentation; Recovery; Regenerative Medicine; Regulation; Replacement Therapy; Retina; Retinal Degeneration; Retinal Diseases; Retinal Photoreceptors; Role; Societies; Source; Testing; Therapeutic; Time; Tissues; Transplantation; UV induced; Ultraviolet Rays; Vascular Endothelial Growth Factors; Vision; Work; autocrine; base; experimental study; fly; functional restoration; genetic approach; human disease; human embryonic stem cell; human embryonic stem cell transplantation; immune activation; improved; induced pluripotent stem cell; insight; macrophage; monocyte; mouse model; neuroprotection; neurotrophic factor; novel therapeutic intervention; paracrine; photoreceptor degeneration; prevent; public health relevance; recruit; regenerative; repaired; response; retinal damage; stem cells; success; tissue regeneration; tissue repair; ultraviolet damage

 DESCRIPTION (provided by applicant): The retina, like many other regions of the nervous system, is subject to a variety of inherited and acquired degenerative conditions. These conditions often result in the degeneration of the photoreceptors, the main light sensing cells in the retina. Despite the loss of photoreceptors, the inner retinal circuitry is intact for many year, and this has led to the possibility of photoreceptor replacement as a potential therapy. Cell replacement strategy is important as the loss of photoreceptors in the mammalian retina is not associated with any effective regeneration from resident cells. A potential source of cellular replacement could be pluripotent stem cells. There are a number of groups looking into the potential of stem cell derived RPE including an approved clinical trial for RPE cell replacement for AMD and Stargardt dystrophy. However, as the disease progresses to vision loss, patients will require replacement of the lost photoreceptor cells as well. Although a number of groups have shown integration of photoreceptors in the mouse retina, the overall efficiency is really low. Additionally, the role of the microglia in this process has largely been unexplored. This proposal aims to look at the role of microglia-derived neurotrophic factors in both retinal repair and regenerative medicine. We will use a cross-species approach to identify and carry out basic studies in flies and apply the result in mammalian retinas.

 描述（由申请人提供）：视网膜，像许多其他区域的神经系统，是受各种遗传和后天变性条件。这些条件通常导致光感受器的变性，光感受器是视网膜中的主要感光细胞。尽管失去了光感受器，但内部视网膜回路多年来都是完整的，这导致了光感受器替代作为潜在治疗的可能性。细胞替换策略是重要的，因为哺乳动物视网膜中光感受器的损失与从驻留细胞的任何有效再生无关。细胞替代的一个潜在来源可能是多能干细胞。有许多小组正在研究干细胞衍生的RPE的潜力，包括一项已批准的用于AMD和Stargardt营养不良的RPE细胞替代的临床试验。然而，随着疾病进展到视力丧失，患者也需要更换丢失的感光细胞。尽管许多研究小组已经证明了小鼠视网膜中的光感受器的整合，但整体效率确实很低。 此外，小胶质细胞在这一过程中的作用在很大程度上尚未探索。该提案旨在研究小胶质细胞源性神经营养因子在视网膜修复和再生医学中的作用。我们将使用跨物种的方法来识别和进行果蝇的基础研究，并将结果应用于哺乳动物视网膜。

项目成果

Small Molecule-Based Retinal Differentiation of Human Embryonic Stem Cells and Induced Pluripotent Stem Cells.

基于小分子的人胚胎干细胞和诱导多能干细胞的视网膜分化。

• DOI: 10.21769/bioprotoc.2882
• 发表时间: 2018
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Zhu,Jie;Lamba,DeepakA
• 通讯作者: Lamba,DeepakA

Generation of Transplantable Retinal Photoreceptors from a Current Good Manufacturing Practice-Manufactured Human Induced Pluripotent Stem Cell Line.

从当前良好生产规范制造的人类诱导多能干细胞系中产生可移植的视网膜感光器。

• DOI: 10.1002/sctm.17-0205
• 发表时间: 2018
• 期刊: Stem cells translational medicine
• 影响因子: 6
• 作者: Zhu,Jie;Reynolds,Joseph;Garcia,Thelma;Cifuentes,Helen;Chew,Shereen;Zeng,Xianmin;Lamba,DeepakAshok
• 通讯作者: Lamba,DeepakAshok