Stem Cell-based therapy for Lymphedema
淋巴水肿的干细胞疗法
基本信息
- 批准号:9102215
- 负责人:
- 金额:$ 40.11万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-01 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAddressAlabamaAnimal ModelBiocompatible MaterialsBiomedical EngineeringBlood VesselsCardiovascular DiseasesCardiovascular systemCell LineageCell SurvivalCell TherapyCell TransplantationCell TransplantsCell physiologyCellsChronicClinicalCommunicable DiseasesDefectDeveloped CountriesDevelopmentDiseaseEdemaEmbryoEngineeringEthicsExtracellular MatrixFaceFailureFibrosisGelGenerationsGoalsGrowthHumanHuman EngineeringImageImmunologicsIncidenceInfectionInflammationInheritedInjectableInnovative TherapyLeadLightLiquid substanceLymphLymphaticLymphatic Endothelial CellsLymphatic vesselLymphedemaMagnetic Resonance ImagingMeasurementMethodsMolecularMorbidity - disease rateOperative Surgical ProceduresPainPeptidesPlayPluripotent Stem CellsProteinsProtocols documentationReportingResearch PersonnelRoleSeriesSerumSomatic CellStagingStem cellsSystemTechniquesTestingTherapeuticTherapeutic EffectTherapeutic InterventionTherapeutic UsesUniversitiesVascular SystemVenousWorkadult stem cellbasebioluminescence imagingcancer radiation therapydesignembryonic stem cellhuman embryonic stem cellin vivoinduced pluripotent stem cellinnovationinsightinterstitialnanostructuredneovascularizationnon-geneticnovelnovel therapeuticspalliativeparacrinepluripotencyprimary lymphedemapublic health relevanceregenerativeresearch studyrestorationstemtranscription factortwo-dimensional
项目摘要
DESCRIPTION (provided by applicant): Lymphedema is the accumulation of lymphatic fluid in the interstitial spaces caused by a defect in the lymphatic vascular system. It is marked by edema, chronic inflammation, and fibrosis, which can lead to painful, disfiguring abnormalities and serious infection. While primary lymphedema occurs infrequently on a hereditary or idiopathic basis, secondary lymphedema is common worldwide, primarily due to infectious disease or radical surgery and radiotherapy for cancer. Despite a continuous increase in the incidence of lymphedema, current therapeutic options are limited to palliative surgical and conservative techniques. Recent progress toward understanding the molecular mechanisms of new lymphatic vessel growth has shed new light on the treatment of lymphedema. Growth factor therapy has yet to show clear clinical benefits in treatment of diseases characterized by deficient arterial or venous vasculature; using a similar strategy to approach lymphedema may face similar hurdles. Recent groundbreaking studies have demonstrated that introduction of pluripotency-associated transcription factors can reprogram somatic cells into embryonic stem (ES)-like cells, referred to as induced pluripotent stem cells (iPSCs). The discovery of iPSCs has presented the opportunity for ES cell-equivalent stem cells to be used therapeutically without concerns about immunologic incompatibility and ethical controversy. Recently, we have developed protocols to efficiently differentiate human iPSCs and ESCs into lymphatic endothelial cell (LEC) lineages. We therefore propose to study the therapeutic effects of hPSC-derived LECs, and their bioengineered derivatives with extracellular matrix-mimicking nanomatrix, on experimental lymphedema. In aim 1, we will develop a novel clinically compatible method to differentiate hPSCs into the lymphatic endothelial lineage and isolate pure hPSC-LECs. In aim 2, we will engineer hPSC-derived LECs with peptide amphiphile-based nanomatrix gel for enhancing cell survival and function. In aim 3, we will determine the effects of
hPSC-derived LECs and their bioengineered constructs on experimental lymphedema. We anticipate that the results of the proposed experiments will yield new insight into the role of novel stem cell-based therapy for treating lymphedema.
描述(由申请方提供):淋巴水肿是由淋巴血管系统缺陷引起的淋巴液在间质中蓄积。它的特点是水肿,慢性炎症和纤维化,这可能导致疼痛,毁容异常和严重感染。虽然原发性水肿很少发生在遗传或特发性基础上,但继发性水肿在世界范围内很常见,主要是由于感染性疾病或根治性手术和癌症放疗。尽管水肿的发生率持续增加,但目前的治疗选择仅限于姑息性手术和保守技术。对新淋巴管生长的分子机制的理解的最新进展为治疗水肿提供了新的思路。生长因子疗法在治疗以动脉或静脉血管缺陷为特征的疾病方面尚未显示出明确的临床益处;使用类似的策略来治疗水肿可能面临类似的障碍。 最近的突破性研究表明,多能性相关转录因子的引入可以将体细胞重编程为胚胎干(ES)样细胞,称为诱导多能干细胞(iPSC)。iPSC的发现为ES细胞等效干细胞提供了治疗性使用的机会,而无需担心免疫不相容性和伦理争议。最近,我们已经开发了将人iPSC和ESC有效分化为淋巴管内皮细胞(LEC)谱系的方案。因此,我们建议研究hPSC衍生的LEC及其具有细胞外基质模拟纳米基质的生物工程衍生物对实验性水肿的治疗作用。在目标1中,我们将开发一种新的临床相容的方法来将hPSC分化为淋巴管内皮谱系并分离纯的hPSC-LEC。在目标2中,我们将用基于肽两亲物的纳米基质凝胶工程化hPSC衍生的LEC以增强细胞存活和功能。在目标3中,我们将确定
hPSC衍生的LEC及其生物工程构建体对实验性水肿的作用我们预计,所提出的实验结果将产生新的见解的作用,新的干细胞为基础的治疗水肿。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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Young-Sup Yoon其他文献
Young-Sup Yoon的其他文献
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{{ truncateString('Young-Sup Yoon', 18)}}的其他基金
Vascular Regeneration with Human Pluripotent Stem Cell-derived Vascular Cells and Engineering Approaches
人类多能干细胞来源的血管细胞的血管再生和工程方法
- 批准号:
10548851 - 财政年份:2022
- 资助金额:
$ 40.11万 - 项目类别:
Vascular Regeneration with Human Pluripotent Stem Cell-derived Vascular Cells and Engineering Approaches
人类多能干细胞来源的血管细胞的血管再生和工程方法
- 批准号:
10366866 - 财政年份:2022
- 资助金额:
$ 40.11万 - 项目类别:
Vascular Regeneration with Direct Reprogramming and Engineering Strategies
直接重编程和工程策略的血管再生
- 批准号:
10530784 - 财政年份:2022
- 资助金额:
$ 40.11万 - 项目类别:
Vascular Regeneration with Direct Reprogramming and Engineering Strategies
直接重编程和工程策略的血管再生
- 批准号:
10641940 - 财政年份:2022
- 资助金额:
$ 40.11万 - 项目类别:
Cardiac Revascularization with Direct Reprogramming Approaches
通过直接重编程方法进行心脏血运重建
- 批准号:
10337071 - 财政年份:2020
- 资助金额:
$ 40.11万 - 项目类别:
Cardiac Revascularization with Direct Reprogramming Approaches
通过直接重编程方法进行心脏血运重建
- 批准号:
9903989 - 财政年份:2020
- 资助金额:
$ 40.11万 - 项目类别:
Human iPSC-derived endothelial cells as Vascular Therapeutics
人 iPSC 衍生的内皮细胞作为血管治疗药物
- 批准号:
10054574 - 财政年份:2020
- 资助金额:
$ 40.11万 - 项目类别:
Human iPSC-derived endothelial cells as Vascular Therapeutics
人 iPSC 衍生的内皮细胞作为血管治疗药物
- 批准号:
10505267 - 财政年份:2020
- 资助金额:
$ 40.11万 - 项目类别:
Cardiac Revascularization with Direct Reprogramming Approaches
通过直接重编程方法进行心脏血运重建
- 批准号:
10557918 - 财政年份:2020
- 资助金额:
$ 40.11万 - 项目类别:
Cardiac Regeneration with Bioengineered Human Stem Cells
利用生物工程人类干细胞进行心脏再生
- 批准号:
9123170 - 财政年份:2016
- 资助金额:
$ 40.11万 - 项目类别:
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