Manipulating Stem Cells to Provide Long Term Regeneration of Irradiated Salivary Glands
Manipulating Stem Cells to Provide Long Term Regeneration of Irradiated Salivary Glands
批准号:
10180935
负责人:
Isabelle M.A. Lombaert
金额:
$35.93万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-01 至 2023-06-30
关键词:
Acinar CellAcinus organ componentAdultAffectAgeAgingAllogenicBinding ProteinsCell LineCell LineageCell MaintenanceCell ProliferationCell TherapyCell TransplantationCellsClinicClinicalClonalityCloningDataDevelopmentDuctal Epithelial CellEpithelialEpithelial CellsFutureGene Expression ProfileGene ProteinsGenesGeneticGlandGoalsHematopoietic stem cellsHeterogeneityHumanImmuneImmunoprecipitationIn VitroKnowledgeLifeLongevityMaintenanceMass Spectrum AnalysisMicroarray AnalysisMolecularMolecular ProfilingMultipotent Stem CellsMusNatural regenerationPainPeer ReviewPopulationProliferatingProto-Oncogene Protein c-kitPublishingQuality of lifeRadiationReporterRoleSalivaSalivarySalivary GlandsSignal TransductionSpeechSubmandibular glandSumSyndromeTaste PerceptionTherapeuticTissuesTranslatingTransplantationTreatment ProtocolsWorkXerostomiabasecancer therapyexperimental studyfetalfetus cellfibroblast growth factor receptor 2bhead and neck cancer patientimprovedin vivoirradiationmouse modelmultipotent cellnovel therapeuticsoral infectionoverexpressionrepairedself-renewalstemstem cell populationstem cell replacementstem cell self renewalstem cell therapystem cellstissue repairtranscription factortranslational approach
中文摘要
项目摘要/摘要
在世界范围内,每年有50多万存活的头颈部癌症患者的生活质量是
由于健康的唾液分泌腺体的共同照射,大大减少了。目前的治疗方法是
抢救唾液过少只能暂时缓解;因此,永久组织修复的新疗法是
需要的。在小鼠模型中,我们通过移植KIT+成功地修复了受辐射的唾液腺
干细胞/祖细胞。然而,这种干细胞/祖细胞的数量随着年龄的增长而减少,
异质性;因此,目前损害了我们有效利用这些细胞进行治疗的能力。近期
我们实验室的发现表明,转录因子Sox10严格调控细胞的增殖和
胎儿KIT+细胞的分化。在这个提议中,我们假设只有成体KIT+细胞亚群,
其中表达Sox10,保留干细胞自我更新能力。因此,我们的目标是:(1)刻画多能性
KIT+细胞群中的干细胞,(2)定义转录因子Sox10在维持成体中的作用
KIT+细胞,以及(3)鉴定人类KIT+细胞的分子异质性和Sox10特征。
总体而言,这里提出的科学想法将扩大我们对唾液腺干细胞群体的了解,
并将显著改善未来以干细胞为基础的疗法拯救唾液过少的情况。
英文摘要
PROJECT SUMMARY/ABSTRACT
Worldwide, the quality of life of over half a million surviving head-and-neck cancer patients per year is
drastically decreased due to co-irradiation of healthy saliva-secreting salivary glands. Current therapies to
rescue hypo-salivation only provide temporary relief; hence new therapies for permanent tissue repair are
needed. In a mouse model, we induced successful repair of irradiated salivary glands by transplanting KIT+
stem/progenitor cells. However, this population of stem/progenitor cells decreases with age and is
heterogeneous; hence, currently compromising our ability to efficiently use these cells for therapy. Recent
discoveries in our lab have shown that transcription factor SOX10 tightly regulates proliferation and
differentiation in fetal KIT+ cells. In this proposal we hypothesize that only a subpopulation of adult KIT+ cells,
which express SOX10, retain stem cell self-renewal capacity. Thus, we aim to: (1) characterize the multipotent
stem cells within the KIT+ cell population, (2) define the role of transcription factor SOX10 in maintaining adult
KIT+ cells, and (3) characterize the molecular heterogeneity and SOX10 signature in human KIT+ cells.
Overall, the scientific ideas proposed here will expand our knowledge of salivary gland stem cell populations,
and will significantly improve future hypo-salivation rescuing by stem cell-based therapies.
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会议论文
Defining the Targets and Function of Direct Trigeminal Sensory Innervation to Salivary Glands
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批准号:10558821
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项目类别:
-
资助金额:$64.32万
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财政年份:2023
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负责人:Isabelle M.A. Lombaert
-
依托单位:
Epigenetic Therapy to Treat Radiation-induced Xerostomia
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批准号:10646364
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项目类别:
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资助金额:$42.41万
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财政年份:2022
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负责人:Isabelle M.A. Lombaert
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依托单位:
Manipulating Stem Cells to Provide Long Term Regeneration of Irradiated Salivary Glands
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批准号:10434885
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项目类别:
-
资助金额:$35.57万
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财政年份:2018
-
负责人:Isabelle M.A. Lombaert
-
依托单位: