Liver Organoid Research: Present Situation, limiting Factors and Future Therapeutical Potential in Pediatric Diseases

S. Bittmann, G. Villalon, E. Moschüring-Alieva, Lara Bittmann, E. Luchter
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Abstract

Organoids are three-dimensional, organ-like cell assemblies in which different cell types have organized themselves in a way that is approximately typical for the corresponding organ in the body. They show three characteristics: self-organization, multicellularity and functionality. The range of organs that can be studied with organoids is growing rapidly and includes the brain, intestine, kidney, stomach, pancreas, lung, liver, prostate, esophagus, gallbladder, and the female reproductive tract, among others, and also the embryo. Organoids are grown either from pluripotent stem cells or from tissue-specific adult stem cells. Adult stem cells are present in a large number of tissues and are responsible for renewing the cells in these tissues. They can only give rise to the cell types that are present in the particular tissue, the stem cell of the intestinal epithelium only produces cells of the intestinal epithelium, but not muscle cells or nerve cells. They are thus multipotent. Today, it is possible to reconstruct organ-like tissue organoids in the laboratory. Stem cells are thereby induced to differentiate by molecular signals and grown in culture systems that promote their three-dimensional self-organization. Rapidly developing organoid technology makes it possible to phenotypically copy cell structure. To some extent, this is also true for the functions of various human organs (for example, brain, thyroid, thymus, intestine, liver, pancreas, stomach, lung, kidney) and even early-stage embryos. As near-physiological 3D culture systems, organoids open up new possibilities to study the development of healthy and diseased organs and offer great potential for translational research. Aims and Objectives: This manuscript concentrates on liver organoid research and its future role in different pediatric diseases.
肝类器官研究:儿科疾病的现状、限制因素和未来治疗潜力
类器官是三维的,类似器官的细胞集合,其中不同类型的细胞以一种近似于体内相应器官的典型方式组织起来。它们表现出三个特征:自组织、多细胞和功能性。可以用类器官进行研究的器官范围正在迅速扩大,包括脑、肠、肾、胃、胰腺、肺、肝、前列腺、食道、胆囊、女性生殖道等,以及胚胎。类器官可以由多能干细胞或组织特异性成体干细胞培养而成。成体干细胞存在于大量的组织中,负责这些组织中的细胞更新。它们只能产生特定组织中存在的细胞类型,肠上皮干细胞只能产生肠上皮细胞,而不能产生肌肉细胞或神经细胞。因此,它们具有多能性。如今,在实验室中重建类器官组织已经成为可能。干细胞通过分子信号诱导分化,并在促进其三维自组织的培养系统中生长。快速发展的类器官技术使细胞结构的表型复制成为可能。在某种程度上,人体各种器官(如脑、甲状腺、胸腺、肠、肝、胰、胃、肺、肾)甚至早期胚胎的功能也是如此。类器官作为一种接近生理的三维培养系统,为研究健康和病变器官的发育开辟了新的可能性,并为转化研究提供了巨大的潜力。目的和目的:这篇论文集中于肝类器官的研究及其在不同儿科疾病中的未来作用。
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