Department of Cytophysiology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland, Medyków 18 str., 40-752, Katowice, Poland.
Students Scientific Society, Department of Cytophysiology, Chair of Histology and Embryology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland, Medyków 18 str., 40-752, Katowice, Poland.
Eur J Pharmacol. 2019 Oct 15;861:172597. doi: 10.1016/j.ejphar.2019.172597. Epub 2019 Aug 10.
Preclinical animal models allow to study development and progression of several diseases, including liver disorders. These studies, for ethical reasons and medical limits, are impossible to carry out in human patients. At the same time, such experimental models constitute an important source of knowledge on pathomechanisms for drug- and virus-induced hepatotoxicity, both acute and chronic. Carbon tetrachloride, D-Galactosamine, and retrorsine are xenobiotics that can be used in immunocompetent animal models of hepatotoxicity, where chemical-intoxicated livers present histological features representative of human viruses-related infection. A prolonged derangement into liver architecture and functions commonly lead to cirrhosis, eventually resulting in hepatocellular carcinoma. In human, orthotopic liver transplantation commonly resolve most the problems related to cirrhosis. However, the shortage of donors does not allow all the patients in the waiting list to receive an organ on time. A promising alternative treatment for acute and chronic liver disease has been advised in liver cell transplantation, but the limited availability of hepatocytes for clinical approaches, in addition to the immunosuppressant regiment required to sustain cellular long-term engraftment have been encouraging the use of alternative cell sources. A recent effective source of stem cells have been recently identified in the human amnion membrane. Human amnion epithelial cells (hAEC) have been preclinically tested and proven sufficient to rescue immunocompetent rodents lethally intoxicated with drugs. The adoption of therapeutic procedures based on hAEC transplant in immunocompetent recipients affected by liver diseases, as well as patients with immune-related disorders, may constitute a successful new alternative therapy in regenerative medicine.
临床前动物模型允许研究几种疾病的发展和进展，包括肝脏疾病。出于伦理和医疗限制，这些研究在人类患者中是不可能进行的。同时，这些实验模型是了解药物和病毒引起的肝毒性的病理机制的重要来源，包括急性和慢性肝毒性。四氯化碳、D-半乳糖胺和 retrorsine 是可用于免疫活性动物肝毒性模型的外源性物质，在这些模型中，化学中毒的肝脏呈现出与人类病毒感染相关的组织学特征。肝脏结构和功能的长期紊乱通常会导致肝硬化，最终导致肝细胞癌。在人类中，原位肝移植通常可以解决与肝硬化相关的大多数问题。然而，供体的短缺使得等待名单上的所有患者都无法及时获得器官。肝细 胞移植被建议作为急性和慢性肝病的一种有前途的替代治疗方法，但由于用于维持细胞长期植入的免疫抑制剂方案以及用于临床方法的肝细胞的有限可用性，人们一直在鼓励使用替代细胞来源。最近在人羊膜膜中发现了一种有前途的干细胞来源。人羊膜上皮细胞 (hAEC) 已经在临床前进行了测试，并被证明足以拯救因药物中毒而致命的免疫活性啮齿动物。在受肝脏疾病和免疫相关疾病影响的免疫活性受者中采用基于 hAEC 移植的治疗程序，可能成为再生医学中一种成功的新替代疗法。
