Nanofiber matrices to improve neural stem cell-mediated cancer therapy
纳米纤维基质改善神经干细胞介导的癌症治疗
基本信息
- 批准号:9160211
- 负责人:
- 金额:$ 32.11万
- 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
- 起止时间:2016-06-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdherenceAffectAllograftingAnimalsApoptoticBiochemicalBiological AssayBloodBrainCaliberCell SurvivalCellsChemotherapy-Oncologic ProcedureClinicClinicalCoculture TechniquesCuesDepositionDextransEngineeringEnzyme-Linked Immunosorbent AssayExcisionFiberGelatinGenetic EngineeringGlioblastomaGrowthHomingHumanImmuneImmune systemIn VitroInjection of therapeutic agentMalignant neoplasm of brainMechanicsMediatingMesenchymal Stem CellsMethodsModelingMovementMusOncogenesOperative Surgical ProceduresPatientsPenetrationPharmaceutical PreparationsPolyestersPolymersPostoperative PeriodPropertyReaction TimeRecurrenceResectedResidual stateSafetySeedsSolidSolventsStem cell transplantStem cellsSurgically-Created Resection CavitySystemTNF-related apoptosis-inducing ligandTNFSF10 geneTestingTherapeuticTissuesTranslatingTransplantationTumor DebulkingWeightXenograft procedureabstractingbiodegradable polymerbioluminescence imagingbrain tissuecancer cellcancer therapycell behaviorcell growthcell typecytotoxicdesigngene productimmunocytochemistryimprovedin vivokillingsmigrationmouse modelnanonanofiberneoplastic cellnerve stem cellnovelnovel therapeuticspreventresponsescaffoldstem cell therapytumor
项目摘要
Project Summary/Abstract
Genetically engineered tumoricidal neural stem cells (tNSCs) are a promising therapy for
the highly aggressive brain cancer Glioblastoma (GBM). Engineered tNSCs have unique
tumor-homing capacity that allows them to deliver anti-cancer gene products directly into
local and invasive GBM foci. We recently discovered that polymeric scaffolds
significantly increase the survival of therapeutic stem cells in the GBM resection cavity,
remained permissive to stem cell tumoritropic homing, and markedly prolong the survival
of mice with post-operative GBM. Yet, limitations to scaffold design are likely to prevent
the effective application of scaffold/tNSC therapy in a clinical setting. Additionally, the
matrix properties that regulate tNSC therapy are unknown, preventing the optimization of
scaffold parameters in order to develop a scaffold/tNSC treatment that is effective
against post-surgical GBM in patients. Our results show that altering fiber diameter and
gelatin doping within scaffolds improves tNSC transplant. This allows us to hypothesize
that optimizing the design features of scaffolds will achieve effective suppression of post-
surgical GBMs by tNSC therapy. We propose to identify the scaffold features that
promote tNSC cancer therapy by using a panel of scaffolds with different biophysical and
biochemical features known to influence stem cell adherence, movement, and
differentiation. We will then determine the ability of scaffolds incorporating multiple
optimized features to improve tNSC therapy using surgical resection models of patient-
derived human xenografts in immune-depleted mice and syngeneic GBM allografts in
immune-competent animals. We propose to undertake the following Aims: 1) Develop
and characterize a panel of polymeric scaffolds with differing topographic, mechanical,
and biochemical properties; 2) Determine the scaffold design parameters that regulate
tNSC therapy for post-operative GBM; 3) Investigate the efficacy and safety of
tumoricidal tSC therapy in immune-competent models of GBM resection/recurrence. The
results of our study will generate a therapeutic tNSC/scaffold transplant strategy capable
of robust GBM killing that can be translated for human patient testing. It will also uncover
the scaffold features that regulate different aspects of tNSCs, allowing us to modulate
tNSC cancer therapy through matrix design.
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)
会议论文数量(0)
专利数量(0)
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Shawn Hingtgen其他文献
Shawn Hingtgen的其他文献
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{{ truncateString('Shawn Hingtgen', 18)}}的其他基金
Harnessing Continuous Liquid Interface 3D Printing to Improve Tumor-homing Stem Cell Therapy for Post-surgical Brain Cancer
利用连续液体界面 3D 打印改善脑癌术后肿瘤归巢干细胞疗法
- 批准号:
10552623 - 财政年份:2022
- 资助金额:
$ 32.11万 - 项目类别:
Harnessing Continuous Liquid Interface 3D Printing to Improve Tumor-homing Stem Cell Therapy for Post-surgical Brain Cancer
利用连续液体界面 3D 打印改善脑癌术后肿瘤归巢干细胞疗法
- 批准号:
10420701 - 财政年份:2022
- 资助金额:
$ 32.11万 - 项目类别:
Engineering stem cell therapies to understand and overcome glioblastoma adaption
工程干细胞疗法以了解和克服胶质母细胞瘤适应
- 批准号:
9447282 - 财政年份:2017
- 资助金额:
$ 32.11万 - 项目类别:
Engineering stem cell therapies to understand and overcome glioblastoma adaption
工程干细胞疗法以了解和克服胶质母细胞瘤适应
- 批准号:
10218274 - 财政年份:2017
- 资助金额:
$ 32.11万 - 项目类别:
Engineering stem cell therapies to understand and overcome glioblastoma adaption
工程干细胞疗法以了解和克服胶质母细胞瘤适应
- 批准号:
9751410 - 财政年份:2017
- 资助金额:
$ 32.11万 - 项目类别:
Nanofiber matrices to improve neural stem cell-mediated cancer therapy
纳米纤维基质改善神经干细胞介导的癌症治疗
- 批准号:
9282732 - 财政年份:2016
- 资助金额:
$ 32.11万 - 项目类别:
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