疾病原发性人类肝细胞在全人类细胞基三培系统中的表征
Justin J Odanga1, Sharon M Anderson1, Erick K Breathwaite1
1Institute of Regenerative Med., LifeNet Health, 1864 Concert Dr., Virginia Beach, VA, USA.
Scientific reports
|March 22, 2024
概括
一个新的TruVivo人体三种植系统有效地模拟了像NAFLD这样的肝脏疾病. 这种平台保留了人类初级肝细胞的关键表型差异,使得更好地研究脂质生成机制.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 在体外建模模型.
- 疾病的病原发生 疾病的病原发生
背景情况:
- 肝脏疾病,包括非酒精性脂肪性肝病 (NAFLD),是一个重大的全球健康挑战.
- 现有的体外模型往往无法维持原发性人肝细胞 (PHH) 形态和功能,限制了疾病研究.
- 需要采用捕获疾病特异性表型的模型,例如脂质积累和炎症酶激活.
研究的目的:
- 在TruVivo全人类三种培养系统 (hTCS) 中,从正常和患病的肝脏中鉴定初级人类肝细胞 (PHHs) 的功能.
- 评估TruVivo系统维持PHH形态和功能的能力,并在两周的培养期内呈现与疾病相关的表型.
主要方法:
- 从正常和患病的肝脏中获得的初级人类肝细胞 (PHHs) 在TruVivo hTCS中培养了两周.
- 分析了代谢功能 (白蛋白,尿素,CYP450活性),巨细胞标记物表达 (CD68,CD163),炎症性细胞因子 (IL-6,MCP-1),纤维化标记物 (CK-18,TGF-β) 和基因表达 (FASN,PCK1,G6PC).
- 使用油酸和高葡萄糖治疗研究了脂质生成和细胞内脂质积累.
主要成果:
- 来自疾病的PHHs显示阿尔伯明,尿素和CYP3A4活性下降,与正常PHHs相比,CYP2E1表达率更高.
- 巨细胞标记物 (CD68,CD163),促炎性细胞因子 (IL-6,MCP-1) 和纤维细胞标记物 (CK-18,TGF-β) 在患病的PHHs中升高.
- 脂原酶 (FASN,PCK1,G6PC) 的基因表达在患病的PHH中减少.
- 在特定培养条件下,在正常和患病的PHH之间观察到脂质生成和脂质积累的差异.
结论:
- 特鲁维沃hTCS维持PHH形态和功能,在两周内保持正常和患病细胞之间的表型差异.
- 这个系统准确地反映了与疾病相关的特征,包括改变的新陈代谢,炎症和纤维化标志物.
- "TruVivo"是一个有前途的平台,用于调查脂质生成机制和研究不同患者群体的肝脏疾病.
相关概念视频
Liver Regeneration
The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Cells of Liver
The liver comprises four major types of cells— hepatocytes, stellate, Kupffer, and sinusoidal endothelial cells. The hepatocytes are large...
Hepatitis
Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...


