Development of platforms for sorting, production, editing of beta cells
Development of platforms for sorting, production, editing of beta cells
批准号:
10682155
负责人:
Amit Choudhary
金额:
$69.15万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-09-05 至 2028-04-30
关键词:
AffinityAnti-Inflammatory AgentsBenchmarkingBeta CellBindingBiologyCRISPR/Cas technologyCadaverCell Culture TechniquesCell LineCell Membrane PermeabilityCell ProliferationCell SurvivalCell TransplantationCell physiologyCell secretionCellsChemicalsClinical TrialsDependenceDevelopmentDyesEncapsulatedEndocrineEngineeringExhibitsFaceFibrosisForeign-Body ReactionGenerationsGenesGeneticGenome engineeringGlucoseGraft RejectionHarmineHumanImmuneImmune systemImmunosuppressive AgentsImpairmentInsulinInsulin-Dependent Diabetes MellitusInterleukin-10IonsIslets of LangerhansIslets of Langerhans TransplantationKnock-inLegal patentLibrariesLifeLigandsMitogensPancreasPatientsPlasmaPopulationPreventionProceduresProdrugsProductionProliferatingPropertyProtein Tyrosine KinaseProtocols documentationQuality of lifeReplacement TherapyReportingSchemeSortingSourceSpecificitySurgical ReplantationSystemTeratomaTherapeuticTherapeutic EffectTimeTransplantationTreatment CostTreatment EfficacyUndifferentiatedUnited States National Institutes of HealthValidationZinccell typechemical conjugatecostcost effectivecytokinedifferentiation protocolelastase inhibitorembryonic stem cellengineered beta cellfluorophoregenome editingglycemic controlimmunoregulationimplantationin vivoinduced pluripotent stem cellinhibitorisletlarge scale productionmouse modelprecise genome editingside effectsmall moleculestem cellstherapeutic developmenttransplantation therapy
中文摘要
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英文摘要
PROJECT SUMMARY
Patients suffering from type 1 diabetes must undergo burdensome, often lifelong, exogenous insulin
dependence. Up to now, the only available replacement therapy is to transplant islets from cadaveric donors.
However, such procedures present hurdles such as the scarcity of available donors and the rejection of
transplanted cells by the patient’s immune system. Also, over time, the transplanted islets tend to die. Several
types of stem cells, including embryonic stem cell and induced pluripotent stem cell, have been extensively
studied to generate glucose-responsive insulin-secreting cells and represents a more tenable source of islets.
However, a significant concern for transplantation therapy is the need for immunosuppressive drugs, which
exhibit long term side effects and hinders the feasibility of this approach to the large population of T1D patients.
Furthermore, cost-effective and large-scale production of these stem cell-derived beta cells is still a major
challenge. We propose to apply chemical biology and genome engineering approaches to develop platforms
for efficient sorting, production, and editing of these beta cells.
PHS 398/2590 (Rev. 06/09) 1 Continuation Format Page
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海外基金