Hydrogel Coated Encapsulation of Cells for Liver Disease Stem Cell Therapy

在英国，肝脏疾病对每年的死亡人数有很大贡献。目前治疗终末期肝病的唯一方法是完全移植，而器官的可用性不足以满足目前的需求。即使移植成功，患者在其余生中仍必须定期服用免疫抑制剂。这一问题的一个潜在替代解决方案是注射包裹细胞作为一种干细胞治疗形式，长期目标是完全非侵入性治愈。值得注意的是，虽然肝脏构成了这个项目的重点，但这种方法并不局限于它。这种方法将在再生医学中有广泛的应用，因为它也可能与肺、关节或心脏的治疗相关。该项目的主要目的是开发一种数学模型，能够量化和预测体内使用水凝胶涂层干细胞预防肝病的有效性。我们将首先推导一个模型，该模型旨在描述水凝胶涂层如何在微观和宏观尺度上影响细胞力学。特别是，我们将确定细胞涂层如何调节细胞从周围粘性流体中感受到的剪应力。然后，这可以扩展到考虑被包裹的细胞的悬浮液如何通过血流输送到肝脏以及随后的植入。在整个项目中，在下文详述的实验合作者的帮助下，这些模型将使用已有的体外和体内数据进行校准和验证。通过创建新的模型来描述细胞/水凝胶的行为，或者通过使用数值方法来创建被包裹的细胞及其与肝脏的相互作用的定制模拟，以及通过应用渐近分析，有很大的空间来确保形成一个新的项目；该项目的内容与EPSRC的几个核心研究领域一致。这类问题本质上是非线性的，将使用连续介质力学作为框架来解决，而大量的应用使得它也自然地属于数学生物学的领域。这个DPhil项目将是与伯明翰和爱丁堡的研究人员合作的一部分。在伯明翰，Alicia El Haj带领一个团队在微流体系统中进行微囊化细胞的体外实验，爱丁堡的MRC再生医学中心将提供动物模型。所有这项实验工作都是由MRC赠款资助的，将为模型验证提供有用的数据。

Liver disease forms a large contribution to the number of annual deaths in the UK. The only current cure for end-stage liver disease is a full transplant and the availability of organs is not sufficient to meet current demands. Even with a successful transplant the patient must still regularly take immunosuppressants for the remainder of their life. A potential alternative solution to this problem is the injection of encapsulated cells as a form of stem cell therapy, with a long-term goal being a completely non-intrusive cure. It is worth noting that while the liver forms the focus of this project, this method is not limited solely to it. This method would have wide applications in regenerative medicine as it could also be relevant to treatment of the lung, joints or the heart. The main aim of this project is to develop a mathematical model that is able to quantify and predict the effectiveness of using hydrogel coated stem cells in vivo to prevent liver disease. We will first derive a model which aims to describe how a hydrogel coating affects a cells mechanics on both the micro and macro-scales. In particular, we will determine how the cell coating modulates the shear stress experienced by the cell from the surrounding viscous fluid. This can then be expanded to consider how a suspension of encapsulated cells are delivered via the blood stream to the liver and their subsequent engraftment. Throughout this project, and with the help of experimental collaborators detailed below, these models will be calibrated and validated using in vitro and in vivo data which is already available. There is much scope for ensuring this forms a novel project; either by the creation of new models to describe the cell/hydrogel behaviour or by employing numerical methods to create a bespoke simulation of the encapsulated cells and their interaction with the liver, as well as through the application of asymptotic analysis.The content of this project aligns with several of the core EPSRC research areas. These kinds of problems are inherently non-linear and will be solved using continuum mechanics as a framework, and the numerous applications cause it to also fall naturally under the area of mathematical biology. This DPhil project will be part of a collaboration with researchers in Birmingham and Edinburgh. In Birmingham, Alicia El Haj leads a team carrying out in vitro experiments of encapsulated cells in micro fluid systems and the MRC Centre of Regenerative Medicine in Edinburgh will provide animal models. All of this experimental work is funded through an MRC grant and will provide useful data for model validation.