Optimization of red blood cells production from iPS cells using CombiCult Technology

我的博士项目将专注于利用Platticell的Combiult技术改善人类诱导多能干细胞(HiPSCs)的红细胞分化过程。髋关节细胞向红细胞的分化是一个复杂的过程，在体外很难概括。这一过程中涉及的主要问题是了解哪些旁分泌和自分泌信号以及细胞因子和其他生长因子参与了红细胞的分化。为了在体外实现更好的红系细胞分化，我的实验室与Platticell公司开展了合作，使用他们的一项新技术-Combiult。这项技术将允许在细胞分化过程中使用不同的介质、细胞因子和生长因子，并使用组合筛选来了解哪种条件是将HIP分化为成熟红系细胞的最佳条件。在这个项目的开始，也是精密医学iCASE计划的一部分，我将在Platticell作为研究员进行为期三个月的实习。这次实习将使我了解Combiult技术的工作原理，包括将髋关节细胞转化为Combiult技术的过程，以及使用公司开发的生物信息学组合方法确定最佳方案的过程。在实习结束时，预计将有必要的方法学来促进髋关节细胞分化为红细胞。目前，该实验室正在进行的主要项目之一是研究髋关节来源的巨噬细胞的红细胞岛，以及这种结构的形成和细胞与细胞的接触如何支持从脐带血细胞产生红细胞性细胞。对于该项目的第二部分，很有兴趣了解红系细胞岛的形成是否促进了红系细胞的分化和/或成熟。这项研究将在工业方法确定的分化条件得到验证后放置在实验室中。已建立的方法的特性也将在Forrester实验室提供的不同iPS细胞系中进行测试。我的项目主要设在小法国的苏格兰再生医学中心(SCRM)，在Lesley Forrester实验室。在这个3.5年的博士课程期间，作为SCRM研究生课程的一部分，我将参加研讨会、讨论小组、科学诱导、研讨会和期刊俱乐部。作为以SCRM为基地的博士生培训的一部分，我将提交一份为期10周的报告，并作为研究所内部研讨会的一部分提交我的项目建议和结果，我将提交一份10个月的项目报告，并在年底(5月或6月)介绍项目进展。

My PhD project will focus on the improvement of the differentiation process of red blood cells from human induced pluripotent stem cells (hiPSCs) using Plasticell's Combicult technology. Differentiation of hiPS cells into erythrocytes is a complex process proven difficult to recapitulate in vitro. The main issues that are involved in this process is the understanding of which paracrine and autocrine signals, along with cytokines and other growth factors, that are involved in the differentiation of red blood cells. In the aim to achieve better differentiation of erythroid cells in vitro, my laboratory has developed a collaboration with Plasticell Company to use one of their new technologies - Combicult. This technology will allow the use of different media, cytokines and growth factors on cell differentiation process and use a combinatorial screen to understand which is the optimal condition to differentiate hiPS in to mature erythroid cells. At the beginning of this project, and part of the Precision Medicine iCase programme, I will have a three months internship at Plasticell as a researcher. This internship will allow me to comprehend how Combicult technology process works, including the procedure with the hiPS cells into the Combicult technology and the identification of the best protocol using bioinformatics combinatorial method developed by the company. At the end of the internship, it is expected to have the necessary methodology to promote hiPS cells differentiation into red blood cells. At the moment, one of the main projects ongoing in the lab is the study of erythroid islands from hiPS derived macrophages, and how the formation of this structure and the cell-cell contact endorse the generation of erythroid cells from cord blood cells. For the second part of the project, would be interesting to understand if the formation of erythroid islands, with cells obtained using Combicult technology, facilitate the differentiation and/or maturation of erythroid cells. This study would be placed in the lab after validation of differentiation conditions that the industrial approach has identified. Characterisation of the established method will be also tested in different iPS cell lines available in the Forrester lab.My project is mostly based in the Scottish Centre for Regenerative Medicine (SCRM), in Little France, in Lesley Forrester Lab. During this 3.5 year of PhD programme and as part of the post-graduate programme in SCRM I will be attending to seminars, discussion groups, science inductions, workshops and journal clubs. As part of the training for PhD student based at the SCRM, I will submit a 10 week report and present my project proposal and results as part of the internal seminars of the institute, I will submit a 10 month report of the project and present the project evolution at the end of the year (May or June).