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:9472452
- 负责人:
- 金额:$ 53.81万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-25 至 2022-06-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAnatomyAnimalsAxonCaliforniaCell TherapyCell TransplantsCellsCervicalCervical spinal cord structureChronicClinical ResearchContusionsCorticospinal TractsDataDevelopmentEsthesiaForelimbFutureGoalsGrowthHandHand functionsHumanInjuryInterneuronsLesionMacacaMagnetic Resonance ImagingMatched GroupMeasuresModelingMonkeysMotor CortexMotor NeuronsMuscleNatural regenerationNervous System TraumaNeurological statusNeuronsPrimatesRecoveryRecovery of FunctionReportingRodentRoleSafetyScienceSeriesSiteSpasticSpinal CordSpinal Cord ContusionsSpinal cord injuryStem cellsSystemTechniquesTechnologyTestingTimeTracerTransfectionTranslatingTranslationsTransplantationWorkanatomical tracingbaseclinically relevantcohortcostefficacy studyembryonic stem cellfunctional outcomeshand rehabilitationhuman embryonic stem cellimprovedmyelinationnerve stem cellnonhuman primatenovelrelating to nervous systemrepairedsafety studyspasticity
项目摘要
PROJECT SUMMARY/ABSTRACT
This is a new multi-PI proposal from our California Spinal Cord Injury (SCI) consortium to continue to translate
exciting results from the transplantation of neural stem cells (NSCs) from rodent to primate, and to evaluate
efficacy and safety in our non-human primate (NHP) cervical contusion SCI model. Our multi-center
consortium has examined recovery of function and its anatomical correlates in a series of studies using a
cervical hemisection model. We have discovered spontaneous and extensive plasticity of the corticospinal tract
(CST) system that had not been appreciated in previous rodent studies. We have developed the first large NHP
model of cervical hemicontusion SCI together with an open-field scoring system and novel in-cage forelimb activity
and hand function tests to evaluate functional outcomes. The wealth of new information and directions speak to
the value of this shared approach to using the very valuable primate model. This project focuses on translation of
our NHP stem cell work.
We now report that neural stem cells (NSCs) derived from human spinal cord grafted early to hemisection sites in
NHP SCI, extend very large numbers of axons over very long distances, and that these transplants appear to
enhance long-term recovery of hand function, and support CST regeneration into the graft. NSCs derived from
the approved human embryonic stem cell H9 (H9 hESCNSCs) also support CST regeneration into spinal cord
grafts in the NHP after SCI. Further, we have advanced our cell therapy strategy to produce the first H9 hESCNSCs
caudalized to move them towards a spinal cord fate, and have shown that transplants of these cells in rodents
promote much more vigorous regeneration of CST axons7. Therefore, in this proposal in NHPs, we will transplant
caudalized hESCNSCs into a contusion lesion at a more chronic and clinically relevant six week time point. We
hypothesize that these grafts will support robust CST regeneration and enhance recovery of forelimb function,
and provide a relay for CST axons to influence forelimb circuitry in the C8-T1 cord. We will use anterograde
and retrograde tracing, IHC and transfection of graft cells and correlate the connectional data with recovery,
and test the long-term survival, safety, and functional effects of these transplants.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
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JACQUELINE C BRESNAHAN其他文献
JACQUELINE C BRESNAHAN的其他文献
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{{ truncateString('JACQUELINE C BRESNAHAN', 18)}}的其他基金
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:
10568090 - 财政年份:2023
- 资助金额:
$ 53.81万 - 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:
10408138 - 财政年份:2018
- 资助金额:
$ 53.81万 - 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:
$ 53.81万 - 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:
$ 53.81万 - 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:
$ 53.81万 - 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:
$ 53.81万 - 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:
$ 53.81万 - 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:
$ 53.81万 - 项目类别:
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