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
基本信息
- 批准号:10420701
- 负责人:
- 金额:$ 46.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:3-Dimensional3D PrintAdvanced DevelopmentAllograftingAnimalsArchitectureBiological AssayBiophysicsBloodBrainCell SurvivalChemotherapy-Oncologic ProcedureClinicalClinical ResearchCoculture TechniquesComplexCustomDepositionEnzyme-Linked Immunosorbent AssayExcisionGelatinGenetic EngineeringGlioblastomaGrowthHomingHumanHuman EngineeringImageImmuneImmune systemImmunocompetentImplantIn VitroInjectionsKineticsLiquid substanceMalignant NeoplasmsMalignant neoplasm of brainMechanicsMethodsMicroscopicModelingModulusMusNeoplasm TransplantationOperative Surgical ProceduresPatientsPenetrationPerformancePharmaceutical PreparationsPostoperative PeriodPrimary Brain NeoplasmsPrintingProductionPropertyRecurrenceResidual TumorsResidual stateResolutionSafetySeedsShapesSolidStatistical Data InterpretationStem cell transplantSurgically-Created Resection CavityTNF-related apoptosis-inducing ligandTechnologyTestingTherapeuticTissuesTranslatingTransplantationVariantXenograft procedureanti-cancerbasebioluminescence imagingbiomaterial compatibilitybrain tissuecancer cellcancer invasivenesscancer stem cellcancer therapyclinically relevantcopolymerdesignfirst-in-humangene producthydrogel scaffoldimmunocytochemistryimprovedin vivomigrationmouse modelnerve stem cellnovelnovel therapeuticsporous hydrogelpreclinical studyrational designresponsescaffoldstem cell therapystem cellstumor
项目摘要
Project Summary/Abstract
Glioblastoma is the most common primary brain tumor and one of the deadliest forms of cancer. Recently, we
found that biocompatible matrices significantly improve the transplant of tumor-homing neural stem cells into
the post-surgical GBM cavity allowing them to deliver anti-cancer gene products that suppress tumor
recurrence. Yet, the optimal scaffold figuration that maximizes tNSC transplant, migration, drug release, and
subsequent GBM kill remain unknown. Using clinically relevant human tNSCs, matrices, and mouse models of
GBM resection/recurrence, we have found that 3D architecture and scaffold composition markedly enhance
tNSC persistence in the surgical cavity. Here in, we hypothesize that optimizing features through unique 3D
printing of custom designed scaffolds will achieve superior suppression of post-surgical GBMs by tNSC
therapy. Leveraging Continuous Liquid Interface Printing (CLIP), a novel continuous fabrication method with
high spatial resolution, we propose to fabricate a panel of 3D matrices with different architectural, biophysical,
and mechanical response features design rationally selected to improve tNSC therapy. We will define the
impact of each design feature on tNSC persistence, homing and killing in vitro and in vivo, then test a final
optimized matrix incorporating the most beneficial features into a single matrix 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) Utilize CLIP to fabricate a panel of 3D
printed matrices with varied design features; 2) Define the impact of 3D design features on tNSC efficacy for
post-operative GBM; 3) Investigate the efficacy and safety of 3D matrix/tNSC 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)
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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:
$ 46.72万 - 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:
$ 46.72万 - 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:
$ 46.72万 - 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:
$ 46.72万 - 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:
$ 46.72万 - 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:
9160211 - 财政年份:2016
- 资助金额:
$ 46.72万 - 项目类别:
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