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Background and Aims: Experimental models using carbon tetrachloride (CCl4) and D-galactosamine (D-GalN) can be used in preclinical assessment of acute liver failure (ALF) therapies. Unfortunately, these models are characterized by different dynamics of liver injury depending on the animal strain, administered hepatotoxin, and its dose. The aim of this study was to compare known rat and mouse models of ALF with a view to their future introduction into preclinical cell therapy experiments. In particular, based on histopathological and molecular changes, we suggested experimental time cut-off points for an effective stem cell therapeutic intervention. Methods: ALF was induced by a single intraperitoneal injection of CCl4 in mice (50 µL/100 g b.w.) and rats (200 µL/100 g b.w.) and D-GalN in mice (150 mg/100 g b.w.) and rats (50 mg/100 g b.w.). Blood and liver samples were collected 12 h, 24 h, 48 h and 7 days after intoxication. Blood morphology, liver function blood tests, histopathological changes, proliferation activity, apoptosis, fibrosis, and gene expression were analysed to assess liver damage. Results: At 12 h, 24 h, and 48 h after CCl4 injection, mouse livers showed moderate inflammatory infiltration and massive pericentral necrosis. In rats treated with CCl4, minor lymphocytic infiltration in the liver parenchyma was seen at 12 h, followed by necrosis that appeared around central veins at 24 h and persisted to 48 h. In D-GalN-injected mice, the first histopathological signs of liver injury appeared at 48 h. In the livers of D-GalN-treated rats, moderate pericentral inflammatory infiltration occurred after 12 h, 24 h, and 48 h, accompanied by increased proliferation and apoptosis. All histological changes were accompanied by decreasing expression of certain genes. In most experimental groups of rats and mice, both histological and molecular parameters returned to the baseline values between 48 h and 7 days after intoxication. Conclusions: In mice and rats with CCl4-induced ALF, signs of liver failure can be seen as early as 12 h and develop to 48 h. In the D-GalN-induced model, mice are more resistant to the hepatotoxic effect than rats (after 12 h), and the early hepatitis phase can be observed much later, after 48 h. These cut-off points seem to be optimal for suppressing inflammation and applying effective stem cell therapy for acute liver injury.

Mesenchymal stem cells (MSCs) have remarkable immunomodulatory properties, low immunogenicity, and paracrine properties as well as the ability to differentiate into multiple cell lines. These properties make them potential candidates for clinical applications in the treatment of neurodegenerative, cardiovascular, and lung diseases, which may be occupational diseases. Preclinical studies using experimental animal models have demonstrated regenerative properties of MSCs in diseases such as silicosis and occupational asthma. Currently, treatment of the novel disease COVID-19 could be enhanced by using MSC therapies. This disease affects many professional groups with great intensity and its consequences might be considered as an occupational disease. It is a significant public health problem and a therapeutic challenge. Despite the development of vaccines against COVID-19, there is growing concern about the emergence of new mutations of the SARS-CoV-2 virus in addition to the known alpha, beta, gamma, and delta variants. There is still no effective COVID-19 treatment and the existing ones only play a supporting role. MSCs offer treatment possibilities as an alternative or complementary therapy. The clinical trials to date using MSCs in patients with COVID-19 give hope for the safe and effective use of this stem cell population. Med Pr. 2021;72(6)

This study aimed to assess the efficacy and safety of the approved in our Hospital thromboprophylaxis algorithm. Thrombotic events, with higher than usual occurrence, are commonly reported in COVID-19 patients. Until now limited data exist to guide the intensity of antithrombotic prophylaxis. We declare that the risk of arterial and venous thromboembolic events in COVID-19, according to our protocol, can be reduced by more carful optimalization of low molecular heparin administration with a good safety profile.

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