Development of complex-human-based organ models

动物模型、切除的人体组织和2D细胞培养是基础研究的黄金标准，用于研究人体的基本生理过程。因此，特别是动物模型已经超出了几十年的讨论。然而，最近，越来越多的批评来自科学关注和越来越多的认识，即解剖学，生理学和免疫学方面的明显物种间相关差异限制了动物对人类状况的预测能力。虽然切除的人体组织和2D细胞培养是基于人类的，但这些缺乏基础研究中更复杂问题的关键复杂性和可行性。 因此，拟议的5年研究计划的短期目标是：（1）生成人体皮肤和支气管上皮的复杂模型。更具体地说，我们将致力于血管和免疫细胞的实施。(2)这些模型将被实施到一个动态灌注平台，使长期的共同培养，并最终模拟人体的生理过程。第三（3），我们将开发基于人体的脂肪和肝脏组织器官模型。开发的器官模型将被全面表征，并与人体器官功能的金标准进行比较。选择这四个器官（皮肤、肺、脂肪组织和肝脏）是因为皮肤和肺组织紧密相连，但对皮肤-肺串扰的了解很少。此外，这两种器官都是许多物质的进入途径，将它们与深层（脂肪组织）和代谢器官（肝脏）共培养将允许更详细地研究人体内异物的相互作用和途径。 拟议的研究计划的长期目标是开发复杂的基于人类的器官模型，这些模型可以结合在类似人类的环境中，旨在尽可能接近地模拟人类生理学。从长远来看，这些模型可能会彻底改变人类的基础研究。 我提出的研究计划将使我的研究小组能够在一个相对年轻但发展迅速的基于人类的器官模型领域向前迈进，并将显著推进组织工程领域。此外，它将使我能够训练尽管基于人类的器官模型是世界范围内的热门话题，但到目前为止，只有少数加拿大实验室致力于开发复杂的基于人类的器官模型。因此，拟议的研究计划将使加拿大处于这一令人兴奋和尖端研究的最前沿。

Animal models, excised human tissue, and 2D cell cultures are the gold standards in basic research to investigate fundamental physiological processes of the human body. As such, especially animal models have been beyond discussion for several decades. Recently however, increasing criticism evolved from scientific concerns and increasing awareness that distinct inter-species related differences with regard to anatomy, physiology and immunology limit the predictive power of animals for the human situation. Although excised human tissue and 2D cell culture are human-based, these lack the critical complexity and viability to more complex questions in fundamental research. Therefore, the short-term objectives of the proposed 5-year program of research are (1) the generation of complex models of the human skin and the bronchial epithelium. More specifically, we will work on the implementation of blood vessels and immune cells. (2) These models will be implemented into a dynamic perfusion platform which enables a long-term co-cultivation and ultimately to emulate physiological processes of the human body. Thirdly (3), we will develop human-based organ models of adipose and liver tissue. The developed organ models will be comprehensively characterized and compared to the gold standard which is human organ functions. These four organs (skin, lung, fatty tissue and liver) have been chosen since skin and lung tissue is closely connected, but very little is understood about the skin-lung crosstalk. Furthermore, both organs serve as entry routes for many substances and a co-cultivation of them with deep (fatty tissue)- and metabolizing organs (liver) will allow to investigate interactions and pathways of foreign substances in the human body in more detail. The long-term of the proposed program of research is the development of complex human-based organ models which can be combined in a human-like setting aiming for models emulating human physiology as closely as possible. In a long-term view, these models may revolutionize fundamental research in human. My proposed program of research will enable my research group to move forward in a relatively young but fast evolving field of human-based organ models and will significantly advance the field tissue engineering. Furthermore, it will allow me to train Although human-based organ models are a hot topic world-wide, so far, only few Canadian labs are working on the development of complex human-based organ models. Hence, the proposed research program will put Canada at the forefront of this exciting and cutting-edge research.