Synthetic substrates for the expansion and differentiation of hPSC-derived NPCs
Synthetic substrates for the expansion and differentiation of hPSC-derived NPCs
批准号:
9181880
负责人:
DAVID A BRAFMAN
金额:
$23.6万
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:
2016-06-01 至 2018-03-31
关键词:
AddressAlzheimer&aposs DiseaseAmyotrophic Lateral SclerosisAnimal Disease ModelsAstrocytesBiochemical GeneticsBioreactorsCell LineCell ProliferationCell TherapyCellsChemicalsChromosomal StabilityDevelopmentDifferentiation and GrowthDiseaseDisease modelElectrophysiology (science)EngineeringEtiologyExtracellular MatrixGlassGoalsGrowthHealth Care CostsHeterogeneityHumanHuntington DiseaseIn VitroLeadLibrariesLifeMethodsModelingMorbidity - disease rateNeuraxisNeurodegenerative DisordersNeuronal DifferentiationNeuronsNeurotransmittersOligodendrogliaParkinson DiseasePluripotent Stem CellsPolymersPopulationPreclinical Drug EvaluationProliferatingPropertyPublic HealthRecombinantsRegenerative MedicineReplacement TherapyResearchSlideSocietiesSourceSpinal Muscular AtrophyStem cellsSupporting CellSuspension CultureSystemTechnologyTherapeuticUnited StatesVariantbasecell growthcell typechemical propertyclinical applicationdesigneffective therapyfunctional grouphigh throughput technologyhuman diseasehuman embryonic stem cellinduced pluripotent stem cellinterestmortalitymultipotent cellnerve stem cellnervous system disorderneuron lossnew therapeutic targetnovelphysical propertyrelating to nervous systemscale upsymptom treatmenttool
中文摘要
项目摘要
英文摘要
PROJECT SUMMARY ABSTRACT
Despite therapeutic advances, neurodegenerative diseases and disorders remain some of the leading causes
of mortality and morbidity in the United States. Therefore, cell-based therapies to replace lost or damaged
neurons or supporting neural cells are of great therapeutic interest. Human neural progenitor cells (hNPCs)
derived from human pluripotent stem cells (hPSCs, including human embryonic stem cells [hESCs] and human
induced pluripotent stem cells [hiPSCs]) can proliferate extensively and differentiate into all the neural lineages
(i.e. neurons, astrocytes, and oligodendrocytes) that compromise the central nervous system (CNS).
Therefore, hNPCs and their differentiated progeny could provide the cellular raw material to model or treat a
variety of nervous system disorders. However, the clinical application of these cells will require (i) defined,
xeno-free conditions for their expansion and neuronal differentiation and (ii) scalable culture systems that
enable their expansion and neuronal differentiation in numbers sufficient for regenerative medicine and drug
screening purposes. To that end, we will use a novel high-throughput approach to systematically screen a
rationally designed library of physicochemically-defined polymers to identify candidate synthetic substrates for
the expansion and neuronal differentiation of hNPCs. Next, we will use these synthetic substrates as the basis
for the engineering of low shear bioreactor-based systems for large-scale hNPC expansion and neuronal
differentiation. The scaled-up cell populations will be assessed for their heterogeneity as well as their cellular,
biochemical, genetic, and electrophysiological properties. The successful completion of this research will
significantly advance the clinical application of hNPCs and their derivatives as it will enable the large-scale
expansion and neuronal differentiation of hNPCs in quantities necessary for disease modeling, drug screening,
and regenerative medicine applications.
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