Assessment of animal experimental models of toxic liver injury in the context of their potential application as preclinical models for cell therapy

• Published in: European journal of pharmacology 2019-10, Vol.861, p.172597, Article 172597
• Main Authors: Czekaj, Piotr, Król, Mateusz, Limanówka, Łukasz, Michalik, Marcin, Lorek, Katarzyna, Gramignoli, Roberto
• Format: Article
• Language: English
• Subjects: Animals; Carbon tetrachloride; Cell therapy; Cell- and Tissue-Based Therapy; Chemical and Drug Induced Liver Injury - pathology; Chemical and Drug Induced Liver Injury - therapy; Disease Models, Animal; Experimental models of hepatotoxicity; Galactosamine; Medicin och hälsovetenskap; Retrorsine; Species Specificity; Stem cells
• ISSN: 0014-2999; 1879-0712; 1879-0712
• DOI: 10.1016/j.ejphar.2019.172597

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. [Display omitted]