Pax4-induced alpha-to-beta cell conversion
Pax4 诱导的 α 细胞向 β 细胞转化
基本信息
- 批准号:9304205
- 负责人:
- 金额:$ 33.86万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-01 至 2019-06-30
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAlpha CellBeta CellBiologicalCell LineCell LineageCell SurvivalCell TherapyCell physiologyCellsClinicClinical TrialsCollaborationsDataDevelopmentDiabetes MellitusFailureFluorescenceFutureGene TransferGeneticGlucagonGraft SurvivalHormonesHumanHypertrophyInsulinInsulin ResistanceInsulin-Dependent Diabetes MellitusInvestigationIslets of LangerhansIslets of Langerhans TransplantationKnock-inLabelLettersMedicalNatural regenerationNon-Insulin-Dependent Diabetes MellitusOperative Surgical ProceduresPancreatectomyPatientsPhenotypeProteinsPublic HealthReplacement TherapyReporterSouth CarolinaTechnologyTherapeuticTransgenic MiceTreatment EfficacyUniversitiesadenoviral-mediatedbasebeta cell replacementblood glucose regulationcell typechronic pancreatitisdesignexperimental studygene therapyimprovedin vivoinnovationisletnew therapeutic targetnovelpancreas developmentpreventresearch and developmentsuccesstherapeutic developmenttherapeutic targettranscription factor
项目摘要
SUMMARY
Cell-based therapy is promising strategy for the cure of insulin deficient diabetes. One of
such strategies, islet transplantation, has achieved remarkable success over the past decade,
but its use is limited due to islet supply and graft survival. Another cell-based strategy is to
regenerate the insulin-producing β-cells from other cell types. In the preliminary studies, we
explored a strategy to regenerate β-cells from the neighboring glucagon-producing α-cells in
pancreatic islets. Specifically, we explored Pax4, a transcription factor critical for the
determination of α- vs β-cell lineage during development, for this purpose. Our data showed
Pax4 gene transfer into αTC1.9 cells, a clonal α-cell line, induced them to adopt β-cell
phenotype. We also found Pax4 gene transfer into primary human islets significantly improved
β-cell function, and had circumstantial evidence indicating Pax4 not only promoted β-cell
survival, but also induced α-to-β cell conversion. Despite the extensive preliminary studies,
more investigations are required in order to fully realize the therapeutic potential of Pax4 and
to thoroughly understand its actions. We thus propose two specific aims in this project: 1) To
investigate whether Pax4 gene transfer into donor human islets improves the therapeutic
efficacy of islet transplantation; and 2) To investigate whether Pax4 induces α-to-β cell
conversion in primary islets and in vivo using lineage-tracing technology. Clearly, the project
will provide important information regarding the therapeutic actions and potential of Pax4 for
diabetes treatment.
总结
以细胞为基础的治疗是治疗胰岛素缺乏型糖尿病的一个很有前途的策略。之一
这种策略,胰岛移植,在过去的十年中取得了显著的成功,
但由于胰岛供应和移植物存活,其使用受到限制。另一个基于细胞的策略是
从其他细胞类型中再生产生胰岛素的β细胞。在初步研究中,我们
探索了一种从邻近的产生胰高血糖素的α细胞中再生β细胞的策略,
胰岛具体地说,我们研究了Pax 4,一种对细胞凋亡至关重要的转录因子。
在发育过程中确定α细胞谱系与β细胞谱系,用于此目的。我们的数据显示
将Pax 4基因导入克隆性α-细胞系αTC1.9,诱导其向β-细胞转化,
表型我们还发现Pax 4基因转移到原代人胰岛中显著改善了
β细胞功能,并有间接证据表明Pax 4不仅促进β细胞
存活,但也诱导α-至-β细胞转化。尽管进行了广泛的初步研究,
为了充分实现Pax 4的治疗潜力,需要进行更多的研究,
彻底了解它的行为。因此,我们提出了两个具体目标:1)
研究Pax 4基因转移到供体人胰岛中是否能提高治疗效果
胰岛移植的疗效; 2)研究Pax 4是否诱导α-至-β细胞
使用谱系追踪技术在原代胰岛和体内转化。显然,该项目
将提供关于Pax 4的治疗作用和潜力的重要信息,
糖尿病治疗
项目成果
期刊论文数量(0)
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{{ truncateString('HONGJU WU', 18)}}的其他基金
Pax4-induced alpha-to-beta cell conversion
Pax4 诱导的 α 细胞向 β 细胞转化
- 批准号:
9173658 - 财政年份:2016
- 资助金额:
$ 33.86万 - 项目类别:
Improving Islet Transplantation Outcome With Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
8545473 - 财政年份:2012
- 资助金额:
$ 33.86万 - 项目类别:
Improving Islet Transplantation Outcome With Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
8245116 - 财政年份:2009
- 资助金额:
$ 33.86万 - 项目类别:
Improving Islet Transplantation Outcome With Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
8049189 - 财政年份:2009
- 资助金额:
$ 33.86万 - 项目类别:
Improving islet transplantation outcome with Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
7797377 - 财政年份:2009
- 资助金额:
$ 33.86万 - 项目类别:
Improving Islet Transplantation Outcome With Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
8446504 - 财政年份:2009
- 资助金额:
$ 33.86万 - 项目类别:
Improving islet transplantation outcome with Akt1
使用 Akt1 改善胰岛移植结果
- 批准号:
7661419 - 财政年份:2009
- 资助金额:
$ 33.86万 - 项目类别:
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