作为3D器官的功能性老鼠和人类肝细胞的长期扩张
Huili Hu1, Helmuth Gehart2, Benedetta Artegiani2
1Oncode Institute, Hubrecht Institute, KNAW (Royal Netherlands Academy of Arts and Sciences), Utrecht, the Netherlands; The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Genetics, School of Basic Medical Sciences, Shandong University, 250012 Jinan, China.
Cell
|December 1, 2018
概括
研究人员开发了一种新的3D器官培养,模仿受伤后的肝脏再生. 这一突破使得实验室内肝细胞增殖的研究成为可能,进步了肝病研究.
科学领域:
- 肝病学和再生医学
- 三维器官培养技术
背景情况:
- 哺乳动物的肝脏再生通过两种不同的途径发生:慢性疾病中的圆细胞反应和急性损伤中的成熟肝细胞增殖.
- 现有的体外模型成功复制了圆细胞反应,但未能捕捉肝细胞在部分肝切除 (PHx) 等急性损伤后的增殖能力.
研究的目的:
- 建立一个长期的3D器官培养系统,能够在体外复制初级肝细胞的增殖反应.
- 描述这些肝细胞有机体的形态,功能和基因表达特征.
- 验证器官在体内模仿肝细胞增殖的能力,特别是在肝损伤后.
主要方法:
- 使用小鼠和人类初级肝细胞开发一种新的长期3D器官培养系统.
- 从单个肝细胞中确定器官,并评估它们的长期稳定性 (几个月).
- 对器官形态,功能,基因表达和转录特征的分析.
- 将人类肝细胞器官植入小鼠体内,以评估它们的生殖能力.
主要成果:
- 从单个小鼠和人类初级肝细胞成功建立了长期的3D器官培养.
- 在长时间的培养期内,有机体保持了关键的形态,功能和基因表达特征.
- 这些器官的转录形状与PHx后发生的肝细胞的转录形状非常相似.
- 植入的人类肝细胞有机体在体内表现出广泛的增殖,反映了肝细胞的自然损伤反应.
结论:
- 开发的3D器官培养系统有效地回顾了肝细胞在急性肝损伤后的增殖反应.
- 这种新的体外模型为研究肝细胞再生提供了强有力的工具,并可能促进肝脏疾病和治疗的研究.
- 该系统成功模拟了老鼠和人类肝细胞的行为,提供了转化潜力.
相关概念视频
01:05Long-term Depression
33.3K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
33.3K
01:03Long-term Depression
3.4K
Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over...
Calcium Ion Concentration Mechanism
If over...
3.4K
01:24Heat and Free Expansion
2.9K
The work done by a thermodynamic system depends not only on the initial and final states but also on the intermediate states—that is, on the path. Like work, when heat is added to a thermodynamic system, it undergoes a change of state, and the state attained depends on the path from the initial state to the final state. Consider an ideal gas cylinder fitted with a piston. When the cylinder is heated at a constant temperature, the gas molecules absorb energy and expand slowly in a...
2.9K
01:22Thermal Expansion
5.7K
The expansion of alcohol in a thermometer is one of many commonly encountered examples of thermal expansion, which is the change in size or volume of a given system as its temperature changes. The most visible example is the expansion of hot air. When air is heated, it expands and becomes less dense than the surrounding air, which then exerts an upward force on the hot air to, for example, make steam and smoke rise, and hot air balloons float. The same behavior happens in all liquids and gases,...
5.7K
01:25Compounds Essential to Human Function
10.3K
The human body is composed of cells that are fundamentally made up of several different molecules. These molecules are essential to carry out all physiological processes in the body and are broadly classified into organic and inorganic based on their chemical structures.
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
Inorganic Compounds Essential to Human Functioning
Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic, i.e., they do not have a carbon-hydrogen bond. Water...
10.3K
01:12Regional Terms
15.5K
Regional terms describe anatomy by dividing the body parts into different regions that contain structures involved in contributing similar functions. Using these terms helps increase the accurate description and identification of the particular region of interest or region affected by the disease.
Primarily, the human body has two major regions, the axial and appendicular regions. The axial region comprises regions from the head to the abdomen and makes up the central body axis. In contrast,...
Primarily, the human body has two major regions, the axial and appendicular regions. The axial region comprises regions from the head to the abdomen and makes up the central body axis. In contrast,...
15.5K