Transplantation of mesenchymal stem cells combined with ozonotherapy in the treatment of experimental liver cirrhosis
Gomel State Medical University, Gomel, Republic of Belarus
Vestnik VGMU. 2018;17(1):81-90.
Objectives. To evaluate the efficacy of experimental liver cirrhosis treatment by transplantation of mesenchymal stem cells (MSCs) as a monotherapy, and also in combination with ozonotherapy.
Material and methods. White Wistar male rats (n=45) were used as an object of our study. After modelling liver cirrhosis (by our own technique) a course of ozonotherapy was performed in one group of rats (group 3). Then the animals of groups 2 and 3 were treated with single intraportal injection of autologous mesenchymal stem cells. Animals were taken out of the experiment before cell therapy, 1 month and 3 months after cell transplantation, morphological and morphometric state of the liver was studied in them with further statistical processing of the results obtained.
Results. In 1 month and 3 months after transplantation of MSCs an improvement of histological picture of the damaged liver in rats, receiving a monotherapy with autologous MSCs (group 2), and in rats, getting cell therapy combined with ozonotherapy was detected. This fact was proved by statistically significant decrease in the thickness of connective tissue septa (р=0,0041), the amount of binucleate cells (р=0,045) and intensity of dystrophic changes in hepatocytes (p=0,038).
Conclusions. Transplantation of autologous mesenchymal stem cells as a monotherapy as well as in combination with ozonotherapy leads to statistically significant improvement of the histological picture of experimental liver cirrhosis both in 1 month and 3 months after cell therapy. Rats, which had got a course of ozonotherapy before transplantation of MSCs, showed statistically better morphometric indices both in 1 month and 3 months period after cell therapy than rats, which had been treated with MSCs only.
Key words: liver cirrhosis, ozonotherapy, mesenchymal stem cells, morphometry, dystrophy, binucleate cells.
1. Scaglione S, Kliethermes S, Cao G, Shoham D, Durazo R, Luke A, et al. The Epidemiology of Cirrhosis in the United States: A Population-based Study. J Clin Gastroenterol. 2015 Sep;49(8):690-6. doi: http://dx.doi.org/10.1097/MCG.0000000000000208
2. Tsochatzis EA, Bosch J, Burroughs AK. New therapeutic paradigm for patients with cirrhosis. Hepatology. 2012 Nov;56(5):1983-92. doi: http://dx.doi.org/10.1002/hep.25915
3. Skuratov AG, Lyzikov AN, Voropaev EV, Bereshchenko VV, Petrenev DR, Osipov BB. The prospects of cell transplantation in liver cirrhosis. V: Aktual'nye voprosy khirurgii: materialy XV s"ezda khirurgov Resp Belarus' (Brest 16-17 okt 2014 g). Brest, RB: Al'ternativa; 2014. Р. 74. (In Russ.)
4. Parola M, Robino G. Oxidative stress-related molecules and liver fibrosis. J Hepatol. 2001 Aug;35(2):297-306.
5. Yankovaya TV, Afanasenkova TE. Assessment of biophysical paramento in patients with chronic liver diseases in the outpatient observation. Vestn SGMA. 2014;(3):69-72. (In Russ.)
6. Cho KA, Ju SY, Cho SJ, Jung YJ, Woo SY, Seoh JY, et al. Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow. Cell Biol Int. 2009 Jul;33(7):772-7. doi: http://dx.doi.org/10.1016/j.cellbi.2009.04.023
7. Zuk PA, Zhu M, Ashjian P, De Ugarte DA, Huang JI, Mizuno H, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002 Dec;13(12):4279-95. doi: http://dx.doi.org/10.1091/mbc.E02-02-0105
8. Avtandilov GG. Medical morphometry. Moscow, RF: Meditsina; 1990. 383 р. (In Russ.)
9. Osipov BB, Lyzikov AN, Skuratov AG, Petrenev DR, Prizentsov AA. Transplantation of mesenchymal stem cells in liver cirrhosis in the experiment [Elektronnyi resurs]. V: Sovremennye tekhnologii v khirurgicheskoi praktike: sb materialov Resp nauch-prakt konf [28 apr 2017 g g Grodno]. Grodno, RB; 2017. R. 154-7. 1 el opt disk. (In Russ.)
10. Lyzikov AN, Osipov BB, Skuratov AG, Petrenev DR, Prizentsov AA. Cell therapy of experimental liver cirrhosis in rabbits. Problemy Zdorov'ia Ekologii. 2017;(1):57-62. (In Russ.)
11. Bulatova IA, Shchekotova AP, Suzdal'tseva KN, Shchekotov VV, Ulitina PV, Zhizhilev EV. Superoxide dismutase and glutathionereductase in chronic hepatitis C and nonalcoholic fatty liver disease. Fundam Issled. 2014;(7 ch 3):455-9. (In Russ.)
Information about authors:
Osipov B.B. – lecturer of the Chair of Surgical Diseases No.1 with the course of Cardiovascular Surgery, Gomel State Medical University.