Rationale. The need to find the most effective ways to restore liver function in cirrhosis. Goal. To evaluate the effectiveness of using cellular technologies in liver cirrhosis in an experiment.Materials and methods. The experiment included 132 individuals of c57black mice aged 12 to 18 weeks. All individuals are divided into 5 groups (30 individuals in group’s №1– №3, №5 and 12 individuals in group №4). Individuals of group 5 were removed from the experiment before it began in order to determine the normal weight of the liver and spleen. A model of liver cirrhosis was created for individuals of groups 1– 4. Group 4 individuals were removed from the experiment 30 days after the model was formed to confirm the presence of liver cirrhosis. Individuals of group 1 were given intravenous stem cells. Individuals of group 2 were intraportally injected with stem cells. Individuals of group 3 were not injected with stem cells. Changes in all three groups were evaluated 30 days after cell therapy.Results. Against the background of cell therapy, the greatest decrease in liver mass is observed in group 2 (intraportal administration of stem cells), where the liver mass exceeds normal values by 7%. In second place is group 1 (intravenous administration of stem cells), where the liver mass is higher than normal by 17%. In group 3, the liver mass exceeds normal values by 25.3%. The spleen mass 30 days after the application of cell technologies in the second group differed from normal values by 0.01 g; in group 1-by 0.06 g; in group 3-by 0.1 g. The level of total protein 30 days after the introduction of stem cells in group 1 increased by 5.9%; in group 2 by 28.8%; in group 3 by 1.1%. Albumin levels increased by 11% in group 1, 33.8% in group 2, and remained unchanged in group 3. The ALT level in group 1 decreased by 32.3%, in group 2 by 48.1%, and in group 3 remained unchanged. The AST level decreased by 7% in group 1, by 25.9% in group 2, and remained unchanged in group 3. Indicators of alkaline phosphatase decreased by 3.9% in group 1, by 14.3% in group 2, and did not improve in group 3.Conclusion. The use of cellular technologies in liver cirrhosis contributes to a faster recovery of liver function when intraportal introduction of cellular structures.
cirrhosis, stem cells, cellular technologies, repair regeneration of hepatic tissue
1. Iwamoto T. Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice. Cell Tissue Res. 2013 Mar;351(3):487- 95. doihttps://doi.org/10.1007/s00441-012-1528-z
2. SekiA. Adipose tissue-derived stem cells as a regenerative therapy for a murine steatohepatitis- induced cirrhosis model. Hepatology. 2013 Sep;58(3):1133-42. doi: 10.1002 / hep.26470
3. Zhang, Z. Stem cell therapies for liver failure and cirrhosis. J Hepatology. 2013 Jul;59(1):183-5. doi:https://doi.org/10.1016/j.jhep.2013.01.018.
4. Russo F. P. Stem cells in liver failure. Best Pract Res Clin Gastroenterol. 2012 Feb;26(1):35-45. doihttps://doi.org/10.1016/j.bpg.2012.01.001.
5. Hayashi H. Animal models for the study of liver fibrosis: new insights from knockout mouse models. Am J PhysiolGastrointest Liver Physiol. 2011 May;300(5):G729-38. doihttps://doi.org/10.1152/ajpgi.00013.2011
6. Skuratov A. G. Tetrahlormetanovaya model’ gepatitaicirrozapecheni u krys. Eksperimental’nayai klinicheskayagastroenterologiya.2012;9:37-40.URL: https://cyberleninka.ru/article/n/tetrahlormetanovaya- model-gepatita-i-tsirroza-pecheni-u-krys. Ssylka aktivna na 06.03.2020. (In Russ).
7. Patent № 2197018 C2. RU. Method for modeling liver cirrhosis / Myshkin V. A., Ibatullina R. B., Savlukov A. I., Simonova N. I., Bakirov A. B. Pabl.16.02.2016. Available at: https://yandex.ru/ patents/doc/RU2197018C2_20030120. Accessed 05.03.2020. (In Russ).
8. Uryvaeva I. V. Stem cell biology and cell technologies.V kn: Pal’cev MA, red. Biologiya stvolovyh kletok i kletochnye tekhnologii. Moscow, RU; 2009;2:211-53. (In Russ).
9. Dolgih M.S. Perspektivy terapii pechenochnoj nedostatochnosti s pomoshch’yu stvolovyh kletok. Biomed Himiya. 2008;54(4):376-91. (In Russ).
10. Petrakova O.S, Chernioglo E.S, Terskih V.V, Kalistratova A.V. Ispol’zovanie kletochnyh tekhnologij v lechenii patologij pecheni. Acta Naturae. 2012;4(3):18-33. (In Russ).
11. Wang Y, Yu X, Chen E, Li L. Liver-derived human mesenchymal stem cells: a novel therapeutic source for liver diseases. Stem Cell Res Ther. 2016 May;7(1):71. doi:https://doi.org/10.1186/s13287-016-0330-3.
12. Terai S., Tsuchiya A. Status of and candidates for cell therapy in liver cirrhosis: overcoming the «point of no return» in advanced liver cirrhosis. J Gastroenterol. 2017;52(2):129-40. doihttps://doi.org/10.1007/s00535-016-1258-1.
13. Mubbacha F., Settmacherb U., Dirschc O., Xiea C., Dahmena U. Bioengineered livers: a new tool for drug testing and a promising solution to meet the growing demand for donor organs. Eur Surg Res. 2016 Jul;57(3-4):224-39. doi:https://doi.org/10.1159/000446211.
14. Nagamoto Y, Takayama K, Ohashi K, Okamoto R, Sakurai F, Tachibana M. Transplantation of a human iPSC-derived hepatocyte sheet increases survival in mice with acute liver failure. J Hepatol 2016 May 14;64(5):1068-1075. Epub 2016 Jan 14. https:// doi.org/10.1016/j.jhep.2016.01.004 Ssylka aktivna na 07.06.2020.
15. Chang N., Ge J, Xiu L, Zhao Z, Duan X, Tian L HuR mediates motility of human bone marrowderived mesenchymal stem cells triggered by sphingosine 1-phosphate in liver fibrosis. J Mol Med (Berl). 2017 Jan;95(1):69-82. doi:https://doi.org/10.1007/s00109-016-1460-x. Ssylka aktivna na 07.06.2020.
