Human Organoid Model To Generate Mucosal Immune Cell Populations

先天淋巴样细胞(ILC)是一种主要存在于肺和肠道等器官内的白细胞。人们对这些细胞非常感兴趣，因为它们已被证明在维持健康、抗击感染和癌症方面发挥着重要作用。此外，在某些情况下，它们也被证明会推动疾病的进展。尽管ILC在体内发挥着多种作用，但数量很少，存在于遥远和难以接触的组织中，因此很难获得足够的细胞来研究它们。这意味着大多数研究人员在他们的研究中转向使用动物，如小鼠，因为通过这种方式更容易获得ILC。该项目旨在建立一种技术，用来产生足够数量的人类ILC用于实验研究，因此可以用来取代对小鼠模型的需求。最近，我们发现有机化合物，这些是在实验室培养在培养皿中的微型器官，能够支持大量人类ILC的产生。我们可以很容易地从血液中获得具有成为ILC(ILC前体)能力的细胞。然后，我们将这些前体细胞添加到微型器官中，在那里它们能够生长并完全发育为ILC。此外，所使用的微型器官的类型对这些细胞的发育也很重要。在迷你肠道中生长的ILC类似于直接取自人类肠道的ILC，而在迷你肺中生长的ILC类似于取自肺部的ILC。通过这个项目，我们的目标是通过详细分析在我们的微型器官中生长的ILC的特征来进一步开发和验证这项技术。这将向科学界保证，这些细胞能够准确地与人体内发现的ILC相似，因此其他科学家可以自信地使用这项技术来培养细胞用于他们的研究。通过这样做，我们的目标是使这项技术被科学界广泛采用，导致在我们的微型器官中产生ILC，以取代在某些研究中使用的小鼠ILC。随着这项技术的进步，能够用这种模型代替老鼠的研究数量也会增加。此外，我们的技术还有一个额外的好处，即由于所使用的细胞取自人类，它们能够更准确地模拟ILC在人类健康和疾病中的作用

Innate lymphoid cells (ILC) are a type of white blood cell that mainly reside inside organs such as the lungs and the gut. There is a lot of interest in these cells as they have been shown to play important roles in maintaining health and in fighting infections and cancer. Additionally, under certain conditions they have also been shown to drive disease progression. Despite their many roles in the body, ILC exist in small numbers in distant and hard to access tissues, so it is difficult to obtain enough cells to study them. This means that most researchers turn to the use of animals, such as mice, for their studies as ILC are much easier to obtain this way. This project aims to establish a technology by which to generate human ILC in sufficient numbers for experimental studies and can therefore be used to replace the need for mouse models. Recently, we discovered that organoids, these are mini-organs grown in the lab in a dish, are able to support the generation of large numbers of human ILC. We can easily obtain cells that have the capacity to become ILC (ILC precursors) from blood. Then, we add these precursor cells to the mini-organs where they are able to grow and fully development into ILC. Moreover, the type of mini-organ used is important for the development of these cells. The ILC grown in mini-guts are similar to ILC taken straight from the human the gut whilst ILC that grow in mini-lungs are similar to those taken from the lung. With this project we aim to further develop and validate this technology by analysing in detail the characteristics of the ILC that grow in our mini-organs. This will provide reassurance to the scientific community that these cells are able to accurately resemble the ILC found in the human body and so other scientists can confidently use this technology to grow cells for their studies.By doing this we aim for this technology to be widely adopted by the scientific community leading to ILC generated in our mini-organs to replace the use of mouse ILC in certain studies. As this technology advances, so will the number of studies in which this model will be able to be used instead of mice. Moreover, our technology has the additional benefit that as the cells being used are taken from humans they are able to more accurately model the roles of ILC in human health and disease