Comparative analysis of regenerative activity of bone marrow cells and total RNA extracted from them in chronic fibrosing liver disease

Abstract

Aim: to conduct a comparative assessment of the effectiveness of liver regeneration occurring after induction of chronic fibrosing liver disease (CFLD) using bone marrow mononuclear cells (BMMCs) and total RNA (tRNA) extracted from BMMCs.Materials and methods. The study involved 140 Wistar rats. CFLD was modeled in 100 rats, of which 25 died. The surviving 75 rats (CFLD formed by the third month) were divided into 3 groups: Group 1 – control (administered with physiological saline); Group 2 – a single injection of tRNA from BMMCs at a dose of 30 μg/100g body weight; Group 3 – a single injection of BMMCs at a dose of (30–35) × 106 cells. The dynamics of regenerative processes in the liver was evaluated based on the animal mortality, dynamics of restoration of biochemical markers (ALAT, ASAT, alkaline phosphatase and total protein) and morphological picture of the liver on the seventh day and after three, six and nine months. The significance of differences in the compared values was determined through Student’s t-test for <0.05.Results. Mortality in Group 1 was 12%, in Groups 2 and 3 – 4%; In Group 1, ALAT and ASAT were restored to normal values after two months, alkaline phosphatase after 3 months, and total protein remained low for over 4 months. In Groups 2 and 3, all hepatic homeostasis markers returned to the values they were before CFLD modeling faster than in Group 1 (after two months). However, in Group 2, the regeneration rate was higher than in Group 3. It was revealed that normalization of functional liver parameters in all groups were ahead of restoration of the histological structure of the liver. Liver defibrotic processes in Group 2 were activated after 3 months, and in Groups 1 and 3 – after 6 months. The histological structure of the liver was restored in Group 2 after 6 months, and in Groups 1 and 3 after 9 months.Conclusion. BMMCs and tRNA extracted from them in biologically effective doses trigger liver regeneration in CFLD. However, regulatory effect from the use of tRNA appears earlier and is more effective.

Keywords

• chronic liver failure
• cirrhosis
• bone marrow mononuclear cells
• total rna
• liver regeneration