Investigating the role of CD44 and immune-neuro signaling mechanisms in neural stem cell responses after spinal cord injury

研究 CD44 和免疫神经信号传导机制在脊髓损伤后神经干细胞反应中的作用

基本信息

  • 批准号:
    10467915
  • 负责人:
  • 金额:
    $ 45.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-06-21 至 2027-05-31
  • 项目状态:
    未结题

项目摘要

Project Summary Spinal cord injury (SCI) results in long-term functional impairments due to loss of cord tissue and limited regeneration. Human neural stem cell (hNSC) transplantation has exciting potential as a treatment for SCI, but the complex interactions between hNSC and the extrinsic microenvironment are poorly understood. The objective of this proposal is to address this gap in knowledge, enabling both optimization of therapeutic donor hNSC transplantation, as well as new insights into in vivo signaling/transcriptional networks, and the consequence of these networks for hNSC localization and fate after SCI. Critical to this is goal is elucidating mechanisms of immune-NSC signaling. Spinal Cord Injury (SCI) causes disruption of the blood-spinal-cord barrier, and a robust influx of serum proteins, including C1q. SCI also results in a multiphasic and prolonged immune response, in which infiltrating and resident immune cells also secrete C1q. We have shown that C1q influx is chemoattractive for transplanted hNSC, inducing hNSC migration towards and clustering at the injury epicenter, and driving hNSC towards an astroglial lineage. Blockade of C1q in vivo releases both migration and lineage selection, and enhances SCI repair and locomotor recovery. We have also shown that C1q directly modulates hNSC migration, proliferation, and differentiation in vitro via a receptor-mediated signaling mechanism. Using an unbiased screen, we identified novel interactions between C1q and five candidate receptors expressed by hNSC. Among these is CD44, a receptor with an established role in regulating cellular behavior. Our published data identify CD44 as a principal mediator of hNSC chemoattraction to C1q in vitro and in vivo, and show that C1q-CD44 signaling also modulates hNSC fate. Further, CD44 deletion in hNSC in an acute transplantation paradigm in vivo enhances SCI repair and locomotor recovery. The central hypotheses of the proposed aims are that C1q-CD44 signaling in NSC alters the NSC transcriptome via CD44-ICD heterochromatin modulation, and that deletion of CD44 in transplanted hNSC after SCI will enhance repair. Aim 1 investigates the effect of CD44 KO on hNSC gene expression at baseline and in response to the CD44 ligands C1q, HA, and osteopontin. Aim 2 tests the effect of CD44 deletion on the repair capacity of hNSC transplanted into the SCI microenvironment, and the dependence of this effect on C1q. Aim 3 investigates the effect of CD44 KO in hNSC on localization and fate in relation to signaling and transcriptional networks in vivo after SCI
项目摘要 脊髓损伤(SCI)由于脊髓组织的丢失和局限性导致长期的功能损害。 再生。人类神经干细胞(HNSC)移植作为治疗癌症的一种令人兴奋的潜力 脊髓损伤,但hNSC与外部微环境之间的复杂相互作用较差 明白了。这项建议的目标是解决知识的这一差距,从而实现既优化 治疗性供者hNSC移植以及体内信号/转录的新见解 网络,以及这些网络对hNSC本地化和SCI后命运的影响。对这一点至关重要 IS的目标是阐明免疫-NSC信号转导机制。 脊髓损伤(SCI)导致血-脊髓屏障的破坏和血清的大量涌入 蛋白质,包括C1q.脊髓损伤还导致多相和长期的免疫反应,其中 浸润性免疫细胞和常驻免疫细胞也分泌C1q。我们已经证明了C1q的流入具有化学吸引力。 对于移植的hNSC,诱导hNSC向损伤中心迁移和聚集,并驱动 HNSC向星形胶质细胞方向发展。体内C1q的阻断释放了迁徙和血统选择, 促进脊髓损伤修复和运动功能恢复。我们还证明了C1q直接调节hNSC 通过受体介导的信号机制在体外进行迁移、增殖和分化。使用 无偏筛选,我们确定了C1q与5个候选受体之间的新相互作用,这些受体由 HNSC。CD44就是其中之一,它是一种在调节细胞行为方面具有既定作用的受体。我们的 已发表的数据表明,CD44是体外和体内hNSC对C1q化学吸引的主要介质, 结果表明,C1q-CD44信号对hNSC的命运也有调节作用。此外,急性期hNSC中CD44缺失 体内移植可促进脊髓损伤修复和运动功能恢复。 提出的目标的中心假设是NSC中的C1q-CD44信号改变NSC CD44-ICD异染色质调控转录组及移植人神经干细胞中CD44基因缺失 脊髓损伤后将加强修复。目的1研究CD44KO对人神经干细胞基因表达的影响。 基线和对CD44配体C1q、HA和骨桥蛋白的反应。Aim 2测试CD44的作用 移植入脊髓微环境的人神经干细胞修复能力的缺失及其依赖关系 对C1q的影响目的3探讨CD44KO在人神经干细胞中的定位及与命运的关系 对脊髓损伤后体内信号和转录网络的影响

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 }}

Aileen J Anderson其他文献

Aileen J Anderson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('Aileen J Anderson', 18)}}的其他基金

Investigating the role of CD44 and immune-neuro signaling mechanisms in neural stem cell responses after spinal cord injury
研究 CD44 和免疫神经信号传导机制在脊髓损伤后神经干细胞反应中的作用
  • 批准号:
    10650327
  • 财政年份:
    2022
  • 资助金额:
    $ 45.03万
  • 项目类别:
Multi-channeled Bridges for Promoting Chronic Spinal Cord Repair
促进慢性脊髓修复的多通道桥
  • 批准号:
    10249977
  • 财政年份:
    2020
  • 资助金额:
    $ 45.03万
  • 项目类别:
Multi-channeled Bridges for Promoting Chronic Spinal Cord Repair
促进慢性脊髓修复的多通道桥
  • 批准号:
    10469553
  • 财政年份:
    2020
  • 资助金额:
    $ 45.03万
  • 项目类别:
Multi-channeled Bridges for Promoting Chronic Spinal Cord Repair
促进慢性脊髓修复的多通道桥
  • 批准号:
    10700124
  • 财政年份:
    2020
  • 资助金额:
    $ 45.03万
  • 项目类别:
Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma
纳米颗粒介导的循环单核细胞和中性粒细胞重编程可减少创伤后炎症介导的损伤
  • 批准号:
    10212226
  • 财政年份:
    2019
  • 资助金额:
    $ 45.03万
  • 项目类别:
Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma
纳米颗粒介导的循环单核细胞和中性粒细胞重编程可减少创伤后炎症介导的损伤
  • 批准号:
    10437650
  • 财政年份:
    2019
  • 资助金额:
    $ 45.03万
  • 项目类别:
Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma
纳米颗粒介导的循环单核细胞和中性粒细胞重编程可减少创伤后炎症介导的损伤
  • 批准号:
    10669080
  • 财政年份:
    2019
  • 资助金额:
    $ 45.03万
  • 项目类别:
Nanoparticle-mediated reprogramming of circulating monocytes and neutrophils to decrease inflammation-mediated damage after trauma
纳米颗粒介导的循环单核细胞和中性粒细胞重编程可减少创伤后炎症介导的损伤
  • 批准号:
    9978712
  • 财政年份:
    2019
  • 资助金额:
    $ 45.03万
  • 项目类别:
Human neural stem cell therapy for the treatment of cervical spinal cord injury (
人类神经干细胞疗法治疗颈脊髓损伤(
  • 批准号:
    8503499
  • 财政年份:
    2013
  • 资助金额:
    $ 45.03万
  • 项目类别:
Human neural stem cell therapy for the treatment of cervical spinal cord injury (
人类神经干细胞疗法治疗颈脊髓损伤(
  • 批准号:
    8727119
  • 财政年份:
    2013
  • 资助金额:
    $ 45.03万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 45.03万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了