CNS Radiation Injury: Regeneration via Human ES Cells
中枢神经系统辐射损伤:通过人类胚胎干细胞再生
基本信息
- 批准号:7619623
- 负责人:
- 金额:$ 32.38万
- 依托单位:
- 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:2007-05-08 至 2012-04-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAdverse effectsAffectBehavior assessmentBehavioralBrainBrain NeoplasmsCancer PatientCell CountCellsChildhoodClinicalCognitiveComplexCorpus CallosumCranial IrradiationDataDemyelinationsDerivation procedureDeteriorationEmbryoGoalsHumanIn complete remissionLeadLearningLeukemia in RemissionLiteratureLymphomaMalignant NeoplasmsMemoryModelingNatural regenerationOligodendrogliaOutcomePathogenesisPatientsPilot ProjectsPopulationProductivityProtocols documentationQuality of lifeRadiationRadiation InjuriesRadiation induced damageRattusRoleSliceSourceStem cellsTimeTissuesTransplantationUnited States National Institutes of Healthage groupbasecerebral atrophycognitive functionexhaustionhuman embryonic stem cellin vivoirradiationmigrationmyelinationprogenitorradiation effectregenerativerepairedrestorationstemyoung adult
项目摘要
DESCRIPTION (provided by applicant): The goal of this project is to investigate the potential of human embryonic stem (hES) cell derived oligoprogenitors as restorative therapy for radiation-induced damage in the brain at the structural and functional levels. The project is based on a substantial body of preliminary data including high yield derivation of oligoprogenitors from human ES cells (NIH approved lines WA-01 and WA-09), survival and differentiation of hES derived progenitors in rat brains, and a quantitative study of the deleterious and irreversible effects of radiation to the adult rat brain. Radiation damage to the brain is a significant clinical problem in cancer management, affecting patients with primary as well as metastatic brain tumors. The effects of radiation to the brain generally occur late (>6-12 months after exposure) and lead to irreversible deterioration in cognitive function. The pathogenesis of late radiation damage is complex, but the pathological outcome is characterized by demyelination and subsequent cerebral atrophy. The radiation model remains essentially unexplored as a possible target for cell replacement despite significant literature pertaining to histopathological changes and the terrible toll on quality of life of the cancer patient. We demonstrate that irradiation results in exhaustion of the cycling oligodendrocyte progenitor pool, with subsequent inability of the brain to replace mature myelinating cells. We have recently developed protocols for the highly efficient differentiation of hES cells into oligoprogenitors. Here we propose to address their potential for repairing radiation damage to the CNS. We will purify the oligoprogenitor populations and perform pilot studies in irradiated rats in an effort to optimize cell numbers, migration, survival and favorable timing of graft placement post irradiation. Once these parameters are elucidated, we will proceed with long term oligoprogenitor or sham grafts in irradiated rats and perform careful behavioral assessments of learning, memory and cognitive tasks, as well electrical studies on brain slices to study conduction across the corpus callosum. We hope to demonstrate the role of hES derived oligoprogenitors in cytoarchitectural restoration of myelination and tissue and behavioral function post radiation. This proposal will use exclusively NIH approved hES lines: WA-01 and WA-09.
描述(由申请人提供):本项目的目的是研究人胚胎干(hES)细胞衍生的寡祖细胞在结构和功能水平上作为辐射诱导的脑损伤的恢复性治疗的潜力。 该项目基于大量的初步数据,包括从人ES细胞(NIH批准的细胞系WA-01和WA-09)中高产量衍生寡祖细胞,hES衍生祖细胞在大鼠脑中的存活和分化,以及辐射对成年大鼠脑的有害和不可逆影响的定量研究。脑辐射损伤是癌症治疗中的一个重要临床问题,影响原发性和转移性脑肿瘤患者。 辐射对大脑的影响通常发生在较晚的时候(照射后>6-12个月),并导致认知功能不可逆转的恶化。 晚期放射损伤的发病机制复杂,但病理结果的特点是脱髓鞘和随后的脑萎缩。放射模型仍然基本上未被探索作为细胞替代的可能靶点,尽管有大量关于组织病理学变化和癌症患者生活质量的可怕损失的文献。我们证明,辐射导致耗尽循环少突胶质细胞祖细胞池,与随后的大脑无法取代成熟的髓鞘细胞。我们最近已经开发了用于将hES细胞高效分化成寡祖细胞的方案。在这里,我们建议解决他们的潜力,修复辐射损伤的中枢神经系统。我们将纯化寡祖细胞群,并在辐照大鼠中进行初步研究,以优化细胞数量、迁移、存活和辐照后移植物放置的有利时机。一旦这些参数被阐明,我们将继续在辐照大鼠中进行长期寡祖或假移植,并对学习、记忆和认知任务进行仔细的行为评估,以及对脑切片进行电学研究以研究胼胝体的传导。我们希望证明hES衍生的寡祖细胞在辐射后髓鞘形成和组织及行为功能的细胞结构恢复中的作用。本提案将仅使用NIH批准的hES细胞系:WA-01和WA-09。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
VIVIANE TABAR其他文献
VIVIANE TABAR的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('VIVIANE TABAR', 18)}}的其他基金
Human Dopamine Grafts in Alpha-Synuclein Models of Parkinson Disease
帕金森病α-突触核蛋白模型中的人多巴胺移植物
- 批准号:
10736403 - 财政年份:2023
- 资助金额:
$ 32.38万 - 项目类别:
Functional analysis of the immune landscape in IDH mutant gliomas
IDH 突变神经胶质瘤免疫景观的功能分析
- 批准号:
10196469 - 财政年份:2021
- 资助金额:
$ 32.38万 - 项目类别:
Modeling pediatric glioma in human ES cells:mechanistic and therapeutic insights
在人类 ES 细胞中模拟儿科神经胶质瘤:机制和治疗见解
- 批准号:
9317449 - 财政年份:2016
- 资助金额:
$ 32.38万 - 项目类别:
The derivation of pituitary cells from human ES cells
从人类 ES 细胞衍生垂体细胞
- 批准号:
9068845 - 财政年份:2015
- 资助金额:
$ 32.38万 - 项目类别:
CNS Radiation Injury: Regeneration via Human ES Cells
中枢神经系统辐射损伤:通过人类胚胎干细胞再生
- 批准号:
8064366 - 财政年份:2007
- 资助金额:
$ 32.38万 - 项目类别:
CNS Radiation Injury: Regeneration via Human ES Cells
中枢神经系统辐射损伤:通过人类胚胎干细胞再生
- 批准号:
7266569 - 财政年份:2007
- 资助金额:
$ 32.38万 - 项目类别:
CNS Radiation Injury: Regeneration via Human ES Cells
中枢神经系统辐射损伤:通过人类胚胎干细胞再生
- 批准号:
7845562 - 财政年份:2007
- 资助金额:
$ 32.38万 - 项目类别:
CNS Radiation Injury: Regeneration via Human ES Cells
中枢神经系统辐射损伤:通过人类胚胎干细胞再生
- 批准号:
7418693 - 财政年份:2007
- 资助金额:
$ 32.38万 - 项目类别:
Radiation Damage Repair in the Brain via Human ES cells
通过人类 ES 细胞修复大脑辐射损伤
- 批准号:
6699641 - 财政年份:2003
- 资助金额:
$ 32.38万 - 项目类别:
Radiation Damage Repair in the Brain via Human ES cells
通过人类 ES 细胞修复大脑辐射损伤
- 批准号:
6602653 - 财政年份:2003
- 资助金额:
$ 32.38万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Research Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Standard Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 32.38万 - 项目类别:
Discovery Early Career Researcher Award
RUI: Evaluation of Neurotrophic-Like properties of Spaetzle-Toll Signaling in the Developing and Adult Cricket CNS
RUI:评估发育中和成年蟋蟀中枢神经系统中 Spaetzle-Toll 信号传导的神经营养样特性
- 批准号:
2230829 - 财政年份:2023
- 资助金额:
$ 32.38万 - 项目类别:
Standard Grant
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 32.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 32.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 32.38万 - 项目类别:
Grant-in-Aid for Scientific Research (C)