The comparative analysis of the effectiveness of stimulation of liver regeneration by bone marrow cells and total RNA of these cells

Extensive liver resection (ELR), performed in a number of surgical operations, refers to a critical injury, which necessitates the improvement of methods of therapy of acute post-resection liver failure.

Aim: to compare the effectiveness of stimulation of regenerative processes in the liver residue after ELR (60–70%) by intraperitoneal administration of lysed aspirate bone marrow cells (BMCs) and total RNA (tRNA) isolated from BMCs.

Materials and methods. This work was performed on 175 rats-male Wistar breed 250–300 g, on 75 of which under the inhalation anesthesia it was reproduced the model of the ELR in three groups of experiments: group 1 – control (administration of isotonic solution after ELR), group 2 – in 3–5 hours after ELR the tRNA from BMCs was intraperitoneally injected at a dose of 30 μg/100 g, group 3 – in 3–5 hours after ELR BMCs was administered intraperitoneally at a dose of 30–35 × 10⁶ cells per rat. Comparative studies of the restorative processes in the liver after the ELR in the three groups were carried out by dynamic control of the mitotic activity of hepatocytes in the liver residue, cytolytic enzymes, total bilirubin and total serum protein, as well as the liver residue (mass) weight.

Results. The tRNA from BMCs and BMCs in the indicated doses prevent the risk of the development of lethal outcomes, and also contribute to an earlier (by 10–14 days) normalization of the functional indices of hepatic homeostasis. However, the tRNA from BMCs, compared with BMCs, has a stronger stimulating effect on the recovery processes: it promotes earlier intensification of mitotic activity of hepatocytes and provides a higher rate of recovery of liver mass.

Conclusion. For the induction of recovery processes in the liver residue after ELR, the preference should be given to the tRNA from BMCs.

1. Kawamura T, Noji T, Okamura K et al. Postoperative Liver Failure: Criteria for Predicting Mortality after Major Hepatectomy with Extrahepatic Bile Duct Resection. Dig Surg. 2018 Feb; 8. doi: 10.1159/000486906.

2. Khan AS, Garcia-Aroz S, Ansari MA et al. Assessment and optimization of liver volume before major hepatic resection: Current guidelines and a narrative review. Int J Surg. 2018 Apr; 52: 74–81.

3. Dahm F, Georgiev P, Clavien PA. Small-for-size syndrome after partial liver transplantation: definition, mechanisms of disease and clinical implications. Am J Transplant. 2005; 5 (11): 2605–2610.

4. Kotel’nikova LP, Budyanskaya IM. Prevention and treatment of complications after liver resection. Vestnik hirurgii im. I.I. Grekova. 2012; 171 (3): 67–71.

5. Panis Y, McMullan DM, Emond JC. Progressive necrosis after hepatectomy and the pathophysiology of liver failure after massive resection. Surgery. 1997; 121: 142–149.

6. El’chaninov AV. Molecular and cellular mechanisms of liver regeneration after Subtotal resec-tion in experiment: autoref. dis. … doct. med. nauk. M., 2017. 41 p.

7. Vivarelli M, Vincenzi P, Montalti R, Fava G, Tavio M, Coletta M et al. ALPPS Procedure for Extended Liver Resections: A Single Centre Experience and a Systematic Review. PLoS One. 2015; 10 (12): 23.

8. Mahnken AH. Current status of transarterial radioembolization. World J Radiol. 2016; 8 (5): 449–459.

9. Nardo B, Vaccarisi S, Pellegrino V, Cannistra M, Barcellona E, Cavallari G. Extracorporeal portal vein arterialization in man after extended hepatectomy to prevent acute liver failure: a case report. Transplant Proc. 2011; 43 (4): 1193–1195.

10. Karvellas CJ, Subramanian RM. Current Evidence for Extracorporeal Liver Support Systems in Acute Liver Failure and Acute-on-Chronic Liver Failure. Crit Care Clin. 2016; 32 (3): 439–451.

11. Baretta GA, Gama Filho O, Toderke EL, Tolazzi AR, Matias JE. Effect of cyclosporine on liver regeneration in partial hepatectomized rats. Acta Cir Bras. 2015; 30 (1): 54–59.

12. D’Espessailles A, Dossi C, Intriago G, Leiva P, Romanque P. Hormonal pretreatment presrvs liver regenerative capacity and minimizes inflamation after partial hepatectomy. Annals of hepatology. 2013; 12 (6): 981–991.

13. Hu C, Shen S, Zhang A, Ren B, Lin F. The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats. Dig Liver Dis. 2014; 6 (10): 928–935.

14. Inokuma T, Yamanouchi K, Tomonaga T, Miyazaki K, Hamasaki K, Hidaka M et al. Curcumin improves the survival rate after a massive hepatectomy in rats. Hepatogastroenterology. 2012; 59 (119): 2243–2247.

15. Qiu YD, Wang S, Yang Y, Yan XP. Omega-3 polyunsaturated fatty acids promote liver regeneration after 90% hepatectomy in rats. World J Gastroenterol. 2012; 18 (25): 3288–3295.

16. Sato T, Yasui O, Kurokawa T, Asanuma Y, Koyama K. Appraisal of intra-arterial infusion of prostaglandin E1 in patients undergoing major hepatic resection report of four case. Tohoku J Exp Med. 2001; 195 (2): 125–133.

17. Gal’perin EI, Dyuzheva TG, Platonova LV et al. Reduction of liver damage in its extensive resection and toxic damage. Annaly hirurgicheskoj gepatologii. 2008; 13 (1): 51–55.

18. Shagidulin M, Onishchenko N, Krasheninnikov M et al. Transplantation liver cells and multipotent mesenchymal stromal cells for correction and treatment of hepatic failure. Medimond International Proceedings. 2010: 83–86.

19. Boyko NV, Golikov AYu, Tarasov VA, Matishov DG. Role of microRNA in regulation of gene activity in eukaryotes. Vestnik yuzhnogo nauchnogo centra RAN. 2011; 7 (3): 69–78.

20. Prasanth KV, Spector DL. Eukaryotic regulatory RNAs: an answer to the genome complexity conundrum. Genes and Development. 2007; 21: 11–42.

21. Friedman RC, Farh KK, Burge CB, Bartel DP. Most mammalian mRNAs are: conserved targets of microRNAs. Genome Res. 2009 Jan; 19 (1): 92–105. doi: 10.1101/gr.082701.108. Epub 2008 Oct 27.

22. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004 Jul; 5 (7): 522–531.

23. Tishevskaya NV, Gevorkyan NM, Babaeva AG, Zaharov YuM et al. The influence of the total mRNA of lymphoid cells of the spleen on erythropoiesis at experimental polycythemia. Rossijskij fiziol. zhurnal im I.M. Sechenova. 2015; 101 (4): 451–456.

24. Babaeva AG, Gevorkyan NM, Tishevskaya NV, Golovkina LL et al. About hematopoietic properties of ribonucleic acid of peripheral blood lymphocytes of patients with true polycythemia and healthy donors. Oncogematologiya. 2015; 2 (10): 58–62.

25. Onishchenko NA. Cytogenetic recapitulation, induced by medical preparations, as the universal stage of formation of urgent protection against damage at organ transplantation. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2016; 60 (4): 148–153.