Central Nervous System Tissue Organogenesis via Precise Growth Factor Tethering
Central Nervous System Tissue Organogenesis via Precise Growth Factor Tethering
批准号:
9093066
负责人:
Nic D Leipzig
金额:
$22.8万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-07-01 至 2018-06-30
关键词:
AdultAnimalsAutomobile DrivingBehaviorBiocompatible MaterialsBiological AssayBiological Neural NetworksBiomedical EngineeringBiomimeticsCellsChemistryChestChimeric ProteinsChitosanChondroitin Sulfate ProteoglycanCicatrixClinicalComplexCuesDNA MethylationDevicesEncapsulatedEngineeringEnvironmentEpitheliumEventFoundationsFutureGoalsGrowthGrowth Factor GeneHydrogelsImplantInjuryLeadLifeMessenger RNAMethodsModelingMolecularMotorNatural regenerationNerve RegenerationNervous System PhysiologyNeural tubeNeuraxisNeuritesNeuronsOrganOrganogenesisOutcomeOutcome MeasurePathway interactionsPatientsPatternPeptidesPluripotent Stem CellsProtein EngineeringProteinsQuality of lifeRat-1RattusRecoveryRecovery of FunctionReportingResearchSensorySignal TransductionSignaling ProteinSiteSpecific qualifier valueSpinal CordSpinal cord damageSpinal cord injurySpinal cord injury patientsStem cellsStructureSubcutaneous TissueSystemTestingTimeTissuesTranslationsTransplantationTransplanted tissueTreatment EffectivenessWorkadult stem cellbasefunctional outcomesimplantationimprovedin vivoinjuredinnovationmethacrylamidemethylation patternmimeticsnerve stem cellnervous system developmentneuroepitheliumneurogenesisprogramsprospectiveprotein metabolitepublic health relevancerelating to nervous systemrepairedresearch studyresponsesafety studysensory inputstem cell differentiationsubcutaneous
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Spinal cord injury (SCI) results in permanent loss of sensory input and motor function below the damaged region of the spinal cord. There is currently no available treatment for SCI to recover lost function. One exciting prospective strategy is the administration of stem cells to regenerate and functionally restore damaged spinal cord tissue. However, this approach is fraught with challenges as delivered cells lack the instructive cues necessary for successful integration and outcomes; most clinical work simply transfuses patients with stem cells which proves insufficient for treating SCI. Biomaterial-based strategies offer a solution to this challenge: rather than expecting the stem cells to integrate on
their own, we can provide them with a support structure and the necessary instructive cues. We have shown that a naturally-derived hydrogel material, methacrylamide chitosan (MAC), can safely encapsulate adult neural stem cells (aNSCs) and provide a biomimetic matrix necessary for in vivo transplantation. Additionally, we can immobilize important lineage-specifying signaling
proteins to this material through a unique application of protein engineering and click chemistry. Recently, we discovered that, when exposed to the subcutaneous environment, aNSCs encapsulated within a MAC-based neural guidance conduit and with a single immobilized neurogenic fusion protein will form developing neural epithelium. This is important, as neural epithelium represents an immature precursor to mature central nervous system (CNS) tissue. Thus, we hypothesize that our engineered conduit could be matured ectopically within the subcutaneous tissue and then transplanted into a damaged spinal cord, where it would develop and integrate with damaged tissue. This new SCI treatment paradigm will be approached through two aims. First, we aim to quantify and substantiate the environment that leads to the formation of nascent neural tubes in constructs implanted in subcutaneous tissue. Second, we aim to improve and implement the subcutaneous- matured construct to treat SCI. As we progress through this project, the information gained will be of use not only to treat SCI but also
to help understand the complex behavior of stem cell-biomaterial interactions.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
2013 Cellular and Molecular Bioengineering (CMBE) Conference
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批准号:8459264
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项目类别:
-
资助金额:$1.0万
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财政年份:2013
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负责人:Nic D Leipzig
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依托单位:
Adaptable Hydrogel Oxygen Delivery Platform for Wound Care
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批准号:8574636
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项目类别:
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资助金额:$35.83万
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财政年份:2013
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负责人:Nic D Leipzig
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依托单位:
海外基金