Targeting Schwann cell exosomes for treating neuropathic pain

靶向雪旺细胞外泌体治疗神经性疼痛

基本信息

  • 批准号:
    10222806
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-10-01 至 2024-09-30
  • 项目状态:
    已结题

项目摘要

It is increasingly evident that Schwann cells (SCs) in the peripheral nervous system (PNS) function as a unit with neurons to regulate sensory function. When the PNS is injured in trauma, SCs become activated for repair. This involves dramatic phenotypic transformation. If this process is abnormal or inhibited, peripheral nerve injury can result in chronic debilitating pain, a problem observed in the general population, including numerous Veterans. Currently available treatment options for chronic neuropathic pain are very limited and fraught with dependency concerns. To address this unmet clinical need, we have developed a novel method for capturing plasma-derived SC exosomes (SCDEs) from rodents that regulate key cellular mechanisms in pain processing. These SCDEs recapitulate some of the bioactivity observed in exosomes collected in medium from cultured primary SCs. The major goal of this research project is to determine whether we can exploit the activity of SCDEs to improve pain outcomes following peripheral nerve injury. To accomplish our goals, three Specific Aims are proposed. In Specific Aim 1, we will determine whether a continuum of neuropathic SCDEs or naïve SCDEs regulate neuronal sprouting and calcium signaling in DRG neurons. We will apply advance technologies including single cell RNA transcriptome profiling so that we can define the response of specific neuronal subpopulations in the DRG to SCDEs. Central to this Aim is our discovery that neuropathic, but not naïve, SCDEs are capable of inducing robust neurite outgrowth that may contribute to maintenance of chronic pain states. We hypothesize that by targeting these SCDEs we will identify key mechanisms for improving pain outcomes following peripheral nerve injury therapeutically. In Specific Aim 2, our goal is to discover novel SCDE cargo, and specifically noncoding microRNAs, that are expressed in neuropathic paradigms. This discovery-based Aim establishes a microRNA (miR) signature in SCDEs that may be associated with pain producing and pain alleviating properties. Using NanoString™ technology to measure miRs in SCDEs, we identified a pain alleviating miR-142-3p in naïve SCDEs. The proposed work should identify the SC source (unmyelinated, myelinated, activated or repair phenotype) in nerves that contributes to SCDEs. In Specific Aim 3, we will assess whether SCDE phenotypes regulate neuropathic pain in vivo. This Aim is based on our exciting preliminary data demonstrating that naïve SCDEs delivered systemically inhibit thermal hyperalgesia after partial nerve ligation. SCDEs have intrinsic features, such as the stability, biocompatibility and stealth capacity when circulating in the blood stream. Studies using miR mimics and inhibitors are planned to discover mechanisms conferred by SCDEs to DRG neurons. We consider this project highly innovative because we target SCs and sensory neurons for treating chronic pain.
越来越明显的是,周围神经系统(PNS)中的雪旺细胞(SC)作为一个单位发挥作用 神经元来调节感觉功能。当 PNS 在外伤中受伤时,SC 就会被激活进行修复。这 涉及戏剧性的表型转变。如果这个过程异常或受到抑制,周围神经损伤可能会发生 导致慢性衰弱性疼痛,这是普通人群(包括许多退伍军人)中观察到的问题。 目前针对慢性神经性疼痛的可用治疗方案非常有限并且充满依赖性 的担忧。为了解决这一未满足的临床需求,我们开发了一种捕获血浆来源的新方法 来自啮齿动物的 SC 外泌体 (SCDE) 调节疼痛处理的关键细胞机制。这些 SCDE 概括了在培养的原代 SC 的培养基中收集的外泌体中观察到的一些生物活性。这 该研究项目的主要目标是确定我们是否可以利用 SCDE 的活性来改善疼痛 周围神经损伤后的结果。为了实现我们的目标,提出了三个具体目标。在 具体目标 1,我们将确定神经病理性 SCDE 或幼稚 SCDE 的连续体是否调节神经元 DRG 神经元中的萌芽和钙信号传导。我们将应用包括单细胞RNA在内的先进技术 转录组分析,以便我们可以定义 DRG 中特定神经元亚群的反应 SCDE。这一目标的核心是我们发现神经病性而非幼稚的 SCDE 能够诱导 强大的神经突生长可能有助于维持慢性疼痛状态。我们假设通过 针对这些 SCDE,我们将确定改善周围神经后疼痛结果的关键机制 治疗上的损伤。在特定目标 2 中,我们的目标是发现新颖的 SCDE 货物,特别是非编码货物 microRNA,以神经病理范式表达。这一基于发现的目标建立了一种 microRNA SCDE 中的 (miR) 特征可能与产生疼痛和减轻疼痛的特性有关。使用 NanoString™ 技术用于测量 SCDE 中的 miR,我们在实验中发现了一种缓解疼痛的 miR-142-3p SCDE。拟议的工作应确定 SC 来源(无髓鞘、有髓鞘、激活或修复) 表型)在导致 SCDE 的神经中。在具体目标 3 中,我们将评估 SCDE 表型是否 调节体内神经病理性疼痛。这个目标是基于我们令人兴奋的初步数据,这些数据表明天真 SCDE 递送可全身抑制部分神经结扎后的热痛觉过敏。 SCDE 具有内在的 特性,例如在血流中循环时的稳定性、生物相容性和隐形能力。研究 计划使用 miR 模拟物和抑制剂来发现 SCDE 赋予 DRG 神经元的机制。我们 我们认为这个项目具有高度创新性,因为我们针对 SC 和感觉神经元来治疗慢性疼痛。

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 }}

WENDY M. CAMPANA其他文献

WENDY M. CAMPANA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('WENDY M. CAMPANA', 18)}}的其他基金

Regulation of Schwann Cell Mitochondria Homeostasis in Painful Peripheral Neuropathy
疼痛性周围神经病中雪旺细胞线粒体稳态的调节
  • 批准号:
    10790951
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
Targeting Schwann cell exosomes for treating neuropathic pain
靶向雪旺细胞外泌体治疗神经性疼痛
  • 批准号:
    10534107
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Targeting Schwann cell exosomes for treating neuropathic pain
靶向雪旺细胞外泌体治疗神经性疼痛
  • 批准号:
    10700060
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Targeting Schwann cell exosomes for treating neuropathic pain
靶向雪旺细胞外泌体治疗神经性疼痛
  • 批准号:
    10065895
  • 财政年份:
    2020
  • 资助金额:
    --
  • 项目类别:
Identifying novel proteins in injured nerves that promote functional regeneration
识别受损神经中促进功能再生的新蛋白质
  • 批准号:
    10382217
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
Identifying novel proteins in injured nerves that promote functional regeneration
识别受损神经中促进功能再生的新蛋白质
  • 批准号:
    10057001
  • 财政年份:
    2018
  • 资助金额:
    --
  • 项目类别:
LRP-1 is a multifunctional regulator during peripheral nerve injury and pain.
LRP-1 是周围神经损伤和疼痛期间的多功能调节剂。
  • 批准号:
    7997169
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
LRP-1 is a multifunctional regulator during peripheral nerve injury and pain.
LRP-1 是周围神经损伤和疼痛期间的多功能调节剂。
  • 批准号:
    8206801
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
LRP-1 is a multifunctional regulator during peripheral nerve injury and pain.
LRP-1 是周围神经损伤和疼痛期间的多功能调节剂。
  • 批准号:
    7744005
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:
LRP-1 is a multifunctional regulator during peripheral nerve injury and pain.
LRP-1 是周围神经损伤和疼痛期间的多功能调节剂。
  • 批准号:
    7466851
  • 财政年份:
    2008
  • 资助金额:
    --
  • 项目类别:

相似海外基金

How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Training Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Standard Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    --
  • 项目类别:
    Studentship
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Operating Grants
New Tendencies of French Film Theory: Representation, Body, Affect
法国电影理论新动向:再现、身体、情感
  • 批准号:
    23K00129
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The Protruding Void: Mystical Affect in Samuel Beckett's Prose
突出的虚空:塞缪尔·贝克特散文中的神秘影响
  • 批准号:
    2883985
  • 财政年份:
    2023
  • 资助金额:
    --
  • 项目类别:
    Studentship
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了