Embryonic Stem Cell Therapy after Cervical Contusion SCI in NHPs
NHP 宫颈挫伤 SCI 后的胚胎干细胞治疗
基本信息
- 批准号:10568090
- 负责人:
- 金额:$ 68.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-01 至 2028-01-31
- 项目状态:未结题
- 来源:
- 关键词:4-AminopyridineAgonistAnatomyAnimal ModelAxonCaliforniaCellsCervicalClustered Regularly Interspaced Short Palindromic RepeatsComplementary DNAContusionsDataDoctor of PhilosophyElectrophysiology (science)ExhibitsFoundationsFutureGoalsGrantHumanIn VitroInjectionsKnowledgeLeadLeadershipLesionLiteratureMacaca mulattaMediatingMethodsMolecularMonkeysMotor CortexMovementMultiple SclerosisMusNatural regenerationNeuronsPTEN genePerformancePharmaceutical PreparationsPositioning AttributePrimatesRattusRecoveryRecovery of FunctionResearchRodentRoleSiteSpinal CordSpinal Cord ContusionsSpinal cord injuryStem cell transplantTechnologyTextTranslationsTransplantationVertebral columnWorkaxon regenerationdesigner receptors exclusively activated by designer drugsembryonic stem cellfunctional improvementfunctional outcomeshuman embryonic stem cellimprovedknock-downmembermotor recoverynerve stem cellneuralneural circuitneural implantnonhuman primatepharmacologicregenerative therapysmall hairpin RNAstem cell fatestem cell therapy
项目摘要
This new application represents a continuation of the California Primate Spinal Cord Research
Consortium project on human embryonic stem cell (hESC) derived neural stem cell
transplantation; our overarching goal is to understand both basic mechanisms of spinal cord
organization and function in non-human primates, and to leverage these and other advances in
developing translational human pro-regenerative therapies. We have made considerable
progress in the last 5 years and now propose new specific aims that will directly bear on the
potential of human neural stem cells (NSCs) to benefit human SCI.
Aim 1: Examine Mechanisms Underlying Graft-Related Functional Improvement: Graft
Silencing with Inhibitory DREADDs. Work in this aim will establish whether functional
recovery observed in non-human primates after grafts of spinalized neural stem cells is related
to graft activation of host neural circuits. This knowledge will be important for human translation.
Aim 2: Determine Whether 4-AP Improves Anatomical and Functional Outcomes After
Neural Stem Cell Grafts There is a vast literature supporting potentially beneficial effects of
4AP in SCI, and 4AP is approved for human use as a conduction-enhancing drug in multiple
sclerosis. This aim will determine whether treatment with neural stem cell grafts plus 4AP
improves anatomical and functional outcomes.
Aim 3: Determine Whether PTEN/SOCS3 Inhibition Improves Host Corticospinal
Regeneration and Functional Outcomes. Rodent studies indicate that functional benefits of
neural stem cell grafts are mediated by formation of host-to-graft-to-host electrophysiological
relays across sites of SCI. These relays require host axon regeneration into grafts. In humans,
corticospinal axons are essential for voluntary movement. This aim will determine whether
inactivation of PTEN/SOCS3 will enhance corticospinal axon regeneration and improve
functional outcomes in primates.
这项新的应用代表了加州灵长类动物脊髓研究的延续
人胚胎干细胞(hESC)衍生神经干细胞的联盟计划
我们的首要目标是了解脊髓的基本机制,
组织和功能,并利用这些和其他进展,
开发人类转化促再生疗法。我们已经取得了可观的
过去五年取得的进展,现在提出新的具体目标,将直接影响到
人类神经干细胞(NSC)对人类SCI有益的潜力。
目的1:研究移植相关功能改善的机制:移植
抑制性DREADD沉默。这方面的工作将确定
在非人灵长类动物中观察到的脊髓神经干细胞移植后的恢复与
移植激活宿主的神经回路这些知识对于人工翻译来说非常重要。
目的2:确定4-AP是否改善术后的解剖和功能结局
神经干细胞移植有大量文献支持神经干细胞移植的潜在有益作用。
4AP在SCI中,并且4AP被批准用于人类作为多种疾病中的传导增强药物。
硬化症这一目标将确定神经干细胞移植物加4AP治疗是否
改善解剖和功能结果。
目的3:确定PTEN/SOCS 3抑制是否改善宿主皮质脊髓
再生和功能结果。啮齿动物研究表明,
神经干细胞移植物通过宿主-移植物-宿主电生理通路的形成来介导
在SCI的站点之间中继。这些中继需要宿主轴突再生到移植物中。在人类中,
皮质脊髓轴突对于随意运动是必需的。这一目标将决定
PTEN/SOCS 3失活将增强皮质脊髓轴突再生,
灵长类动物的功能结果。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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JACQUELINE C BRESNAHAN其他文献
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{{ truncateString('JACQUELINE C BRESNAHAN', 18)}}的其他基金
Translational Outcomes Project: Visualizing Syndromic Information and Outcomes for Neurotrauma (TOP-VISION)
转化结果项目:可视化神经创伤的症状信息和结果 (TOP-VISION)
- 批准号:
10408138 - 财政年份:2018
- 资助金额:
$ 68.67万 - 项目类别:
Translational Outcomes Project: Visualizing Syndromic Information and Outcomes for Neurotrauma (TOP-VISION)
转化结果项目:可视化神经创伤的症状信息和结果 (TOP-VISION)
- 批准号:
10092617 - 财政年份:2018
- 资助金额:
$ 68.67万 - 项目类别:
Translational Outcomes Project: Visualizing Syndromic Information and Outcomes for Neurotrauma (TOP-VISION)
转化结果项目:可视化神经创伤的症状信息和结果 (TOP-VISION)
- 批准号:
10199067 - 财政年份:2018
- 资助金额:
$ 68.67万 - 项目类别:
Embryonic stem cell therapy after cervical contusion SCI in NHPs
NHP 宫颈挫伤 SCI 后的胚胎干细胞治疗
- 批准号:
9472452 - 财政年份:2017
- 资助金额:
$ 68.67万 - 项目类别:
Embryonic stem cell therapy after cervical contusion SCI in NHPs
NHP 宫颈挫伤 SCI 后的胚胎干细胞治疗
- 批准号:
10210306 - 财政年份:2017
- 资助金额:
$ 68.67万 - 项目类别:
Plasticity and Regeneration in the Primate Spinal Cord
灵长类脊髓的可塑性和再生
- 批准号:
8438429 - 财政年份:2011
- 资助金额:
$ 68.67万 - 项目类别:
Plasticity and Regeneration in the Primate Spinal Cord
灵长类脊髓的可塑性和再生
- 批准号:
8318074 - 财政年份:2011
- 资助金额:
$ 68.67万 - 项目类别:
Plasticity and Regeneration in the Primate Spinal Cord
灵长类脊髓的可塑性和再生
- 批准号:
8640211 - 财政年份:2011
- 资助金额:
$ 68.67万 - 项目类别:
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