Construction of an in vitro lymphoid organoid: studying innate-adaptive immune cell interaction in a 3D culture system

体外淋巴类器官的构建：研究 3D 培养系统中的先天适应性免疫细胞相互作用

• 批准号: BB/F001142/1
• 负责人: Amir Ghaemmaghami
• 金额: $ 43.29万
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FF001142%2F1
• 关键词: Construction; vitro; lymphoid; organoid; studying

The immune system is made up of two components, innate and adaptive. Innate immune cells, mainly dendritic cells, fight pathogens using defences that are quickly mobilised and triggered by cell surface molecules (receptors) that recognise a broad spectrum of pathogens. Adaptive immune cells, such as T cells, on the other hand provide a more specific and long-term protection against pathogens. Although the classification of immunity into innate and adaptive has served to simplify and facilitate the description of many immunological events, it is becoming increasingly evident that the interaction between innate and adaptive immune cells is crucial for mounting appropriate immune responses. This, therefore, necessitated the establishment of suitable culture systems and animal models for studying such interactions, and the use of these systems has so far been useful in understanding the interrelationships between dendritic cells and T cells. However, in trying to better recreate what happens in the human lymph nodes (the small organs where dendritic cells and T cells meet), we are proposing to construct a three-dimensional culture system that resembles a lymphoid organoid. This will hopefully be a more physiological system and one that will allow the development of further applications for studying cell-cell interactions. If successful, this system will eventually reduce the number of some animal experimentations. The development of such a system is timely given that the 7th amendment to the EU Cosmetics Directive will impose a marketing ban on new ingredients tested on animals from 2009 onwards. Our initiative is supported by Unilever, a company which has considerable experience and vested interest in the development of model systems for predicting the allergenic potential of new healthcare products.

免疫系统由先天性和适应性两个部分组成。先天免疫细胞（主要是树突状细胞）利用防御系统来对抗病原体，这些防御系统由识别广泛病原体的细胞表面分子（受体）快速动员和触发。另一方面，适应性免疫细胞，例如 T 细胞，可以针对病原体提供更具体、更长期的保护。尽管将免疫分为先天性和适应性免疫有助于简化和促进许多免疫事件的描述，但越来越明显的是，先天性免疫细胞和适应性免疫细胞之间的相互作用对于产生适当的免疫反应至关重要。因此，需要建立合适的培养系统和动物模型来研究这种相互作用，并且迄今为止，这些系统的使用对于理解树突状细胞和 T 细胞之间的相互关系很有用。然而，为了更好地重现人类淋巴结（树突状细胞和 T 细胞相遇的小器官）中发生的情况，我们建议构建一个类似于淋巴类器官的三维培养系统。这有望成为一个更符合生理学的系统，并且可以开发用于研究细胞间相互作用的进一步应用。如果成功的话，这个系统最终将减少一些动物实验的数量。鉴于欧盟化妆品指令第 7 次修正案将从 2009 年起对经过动物测试的新成分实施销售禁令，因此开发这样一个系统是及时的。我们的计划得到了联合利华的支持，该公司在开发用于预测新保健产品的过敏潜力的模型系统方面拥有丰富的经验和既得利益。

项目成果

Label-free molecular imaging of immunological synapses between dendritic and T cells by Raman micro-spectroscopy.

通过拉曼显微光谱对树突状细胞和 T 细胞之间的免疫突触进行无标记分子成像。

• DOI: http://dx.10.1039/c0an00508h
• 发表时间: 2010
• 期刊: The Analyst
• 作者: Zoladek AB

Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity.

层粘连蛋白和纤连蛋白处理导致产生具有卓越内吞能力的树突状细胞。

• DOI: http://dx.10.1371/journal.pone.0010123
• 发表时间: 2010
• 期刊: PloS one
• 影响因子: 3.7
• 作者: García

Interconnectivity and permeability of supercritical fluid-foamed scaffolds and the effect of their structural properties on cell distribution

超临界流体泡沫支架的互连性和渗透性及其结构特性对细胞分布的影响

• DOI: 10.1016/j.polymer.2013.09.041
• 发表时间: 2014-01-14
• 期刊: Polymer
• 影响因子: 4.6
• 作者: Y. Reinwald;R. Johal;A. Ghaemmaghami;F. Rose;S. Howdle;K. Shakesheff
• 通讯作者: K. Shakesheff

Post-processing of polymer foam tissue scaffolds with high power ultrasound: a route to increased pore interconnectivity, pore size and fluid transport.

用高功率超声波对聚合物泡沫组织支架进行后处理：增加孔隙互连性、孔径大小和流体传输的途径。

• DOI: 10.1016/j.msec.2013.07.046
• 发表时间: 2013-02-18
• 期刊: Materials science & engineering. C, Materials for biological applications
• 作者: N. Watson;R. Johal;Z. Glover;Yvonne Reinwald;Lisa J. White;Amir M. Ghaemmaghami;Stephen P. Morgan;F.R.A.J. Rose;M. Povey;Nick G. Parker
• 通讯作者: Nick G. Parker

Cellular in Vitro Testing: Methods and Protocols

细胞体外测试：方法和方案

• 发表时间: 2014
• 作者: Haycock; John W.; Ahluwalia; Arti; Wilkinson; J. Malcolm
• 通讯作者: J. Malcolm