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Characterising embryonic stem cell-derived tenocytes and defining the changing role of scleraxis during tendon development

表征胚胎干细胞衍生的肌腱细胞并定义巩膜在肌腱发育过程中的作用变化

基本信息

批准号：
1804772
负责人：
金额：
--
依托单位：
University of Cambridge
依托单位国家：
英国
项目类别：
Studentship
财政年份：
2016
资助国家：
英国
起止时间：
2016 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=studentship-1804772
关键词：
Characterising embryonic stem cell derived

项目摘要

Theme: Bioscience for HealthTo aid adult tendon regeneration and reduce the frequency of re-injury novel strategies are being developed which use stem cells that have the potential to differentiate into tenocytes. However, during normal adult tendon repair there is already a substantial influx of tenocytes which produce scar tissue. It is therefore important to design cell therapies that can mimic fetal tenocytes and recapitulate scar-less regeneration. We have shown that equine ESCs differentiate into tenocytes following their injection into the injured horse tendon. Using an in vitro 3D culture system to generate artificial tendons, we have identified transforming growth factor beta 3 and mechanical force as key drivers of differentiation. However, whether ESC-derived tenocytes represent adult or fetal cells is unknown. In this PhD the student will exploit new ways of working by performing global gene expression analyses on ESC-derived, adult and fetal tenocytes. Bioinformatics approaches will be used to determine the developmental stage that ESC-tenocytes represent. Global gene expression analyses will also be performed on cells that are engineered to have knocked down scleraxis levels to identify genes that are downstream of scleraxis regulation. Our synthetic cell culture system to generate artificial tendons will be used and the student will have the opportunity to refine this model by employing bioengineering techniques to apply forces to the tendons to better mimic the in vivo situation. The results of this project will provide novel information to inform future experimental and clinical studies on the application of cell based-therapies for modulating tendon regeneration. ENWW:- data driven biology (bioinformatics)- global gene expression analyses- biological imaging of cells - synthetic biology (3D culture, cell genetic engineering)- statistical analysis of various experimental data

布景主题：为了帮助成人肌腱再生和减少再损伤的频率，正在开发新的策略，这些策略使用具有分化成肌腱细胞潜力的干细胞。然而，在正常的成人肌腱修复过程中，已经有大量的肌腱细胞流入，产生瘢痕组织。因此，重要的是设计细胞疗法，可以模仿胎儿腱细胞和重演无瘢痕再生。我们已经证明，马胚胎干细胞分化成肌腱细胞后，他们注射到受伤的马肌腱。使用体外3D培养系统生成人工肌腱，我们已经确定转化生长因子β 3和机械力是分化的关键驱动因素。然而，ESC衍生的腱细胞是否代表成人或胎儿细胞是未知的。在这个博士学位的学生将通过执行全球基因表达分析ESC衍生的，成人和胎儿肌腱细胞的工作新方法。生物信息学方法将用于确定ESC-腱细胞所代表的发育阶段。还将对经工程改造以敲低巩膜轴水平的细胞进行全局基因表达分析，以鉴定巩膜轴调控下游的基因。将使用我们的合成细胞培养系统来生成人工肌腱，学生将有机会通过采用生物工程技术来对肌腱施加力以更好地模拟体内情况来完善该模型。该项目的结果将提供新的信息，以告知未来的实验和临床研究的应用细胞为基础的治疗调节肌腱再生。ENWW：-数据驱动生物学（生物信息学）-全球基因表达分析-细胞生物成像-合成生物学（3D培养，细胞基因工程）-各种实验数据的统计分析