Harrison Sean Philip, Baumgarten Saphira Felicitas, Verma Rajneesh, Lunov Oleg, Dejneka Alexandr, Sullivan Gareth John
Hybrid Technology Hub-Center of Excellence, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Department of Pediatric Research, Oslo University Hospital, Oslo, Norway.
Front Med (Lausanne). 2021 May 5;8:574047. doi: 10.3389/fmed.2021.574047. eCollection 2021.
Liver cell types derived from induced pluripotent stem cells (iPSCs) share the potential to investigate development, toxicity, as well as genetic and infectious disease in ways currently limited by the availability of primary tissue. With the added advantage of patient specificity, which can play a role in all of these areas. Many iPSC differentiation protocols focus on 3 dimensional (3D) or organotypic differentiation, as these offer the advantage of more closely mimicking systems including; the formation of tissue like architecture and interactions/crosstalk between different cell types. Ultimately such models have the potential to be used clinically and either with or more aptly, in place of animal models. Along with the development of organotypic and micro-tissue models, there will be a need to co-develop imaging technologies to enable their visualization. A variety of liver models termed "organoids" have been reported in the literature ranging from simple spheres or cysts of a single cell type, usually hepatocytes, to those containing multiple cell types combined during the differentiation process such as hepatic stellate cells, endothelial cells, and mesenchymal cells, often leading to an improved hepatic phenotype. These allow specific functions or readouts to be examined such as drug metabolism, protein secretion or an improved phenotype, but because of their relative simplicity they lack the flexibility and general applicability of tissue culture. In the liver field these are more often constructed rather than developed together organotypically as seen in other organoid models such as brain, kidney, lung and intestine. Having access to organotypic liver like surrogates containing multiple cell types with like interactions/architecture, would provide vastly improved models for disease, toxicity and drug development, combining disciplines such as microfluidic chip technology with organoids and ultimately paving the way to new therapies.
源自诱导多能干细胞（iPSC）的肝细胞类型具有以目前受原代组织可用性限制的方式研究发育、毒性以及遗传和传染病的潜力。具有患者特异性这一额外优势，这在所有这些领域都能发挥作用。许多iPSC分化方案侧重于三维（3D）或器官型分化，因为这些具有更紧密模拟系统的优势，包括形成类似组织的结构以及不同细胞类型之间的相互作用/串扰。最终，此类模型有可能用于临床，并且可以与动物模型一起使用，或者更恰当地替代动物模型。随着器官型和微组织模型的发展，将需要共同开发成像技术以实现其可视化。文献中报道了多种被称为“类器官”的肝脏模型，从单一细胞类型（通常是肝细胞）的简单球体或囊肿到在分化过程中包含多种组合细胞类型（如肝星状细胞、内皮细胞和间充质细胞）的模型，这通常会导致改善的肝脏表型。这些模型允许检查特定功能或读数，如药物代谢、蛋白质分泌或改善的表型，但由于其相对简单性，它们缺乏组织培养的灵活性和普遍适用性。在肝脏领域，这些模型更多是构建而成，而不是像在脑、肾、肺和肠等其他类器官模型中那样通过器官型共同发育。获得包含多种具有类似相互作用/结构的细胞类型的器官型肝脏替代物，将为疾病、毒性和药物开发提供大大改进的模型，将微流控芯片技术等学科与类器官相结合，最终为新疗法铺平道路。
