STEM CELL CORRECTION OF TOXIC LIVER LESIONS

Cover Page

Cite item

Full Text

Abstract

Assessment of the feasibility of fetal liver cells (FLC) for correction of a CCl4-induced acute toxic hepatitis was performed. Exposure to

Cl4 in a dose of 3000 mg/kg caused well-defined centrilobular necrosis, hydropic, protein, carbohydrate, and adipose degeneration, as well as vascular disorders. The dynamics of morphological changes in the liver was studied, and the role of their intrinsic regenerative potential was assessed using pathomorphological, histochemical, and immunofluorescence methods. Phenotyping the cellular material was carried out to reveal expression of endodermal and mesodermal markers characteristic for the hepatic epithelium, hematopoietic stem cells, and mesenchymal cells. Three days after FLC transplantation, slowing down of necrotic and dystrophic processes in the liver parenchyma was observed. In some animals, the trabecular structure of the central hepatic zones was restored and, by 5th to 7th day of post-implantation, vascular disorders were eliminated. The resulting data can be considered as evidence for the use of fetal liver cells in the treatment of acute toxic hepatitis.

 

About the authors

G. A. Protasova

Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency

Author for correspondence.
Email: GalaSR@mail.ru

Protasova Galina Arkad’evna

188663, p.o. Kuz’molovsky, Vsevolozhsky District, Leningrad Region

Russian Federation

L. V. Shabasheva

Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency

Email: shabash69@gmail.com

Shabasheva Liliya Vladimirovna

188663, p.o. Kuz’molovsky, Vsevolozhsky District, Leningrad Region

Russian Federation

V. B. Popov

Research Institute of Hygiene, Occupational Pathology and Human Ecology, Federal Medical Biological Agency

Email: vpopovlr@mail.ru

Popov Vadim Borisovich

188663, p.o. Kuz’molovsky, Vsevolozhsky District, Leningrad Region

Russian Federation

References

  1. Kinzirskaya Yu.A., Bogush T.A., Ostapchuk N.V., Fisenko V.P. Hepatotoxic action of drugs of some pharmacological groups. Clinical medicine. 2003; 10: 11-16 (in Russian).
  2. Browning J.D. et al. Prevalence of Hepatic Steatosis in an Urban Population in the United States: Impact of Ethnicity. Hepatology. 2004; 40 (6): 1387-1395.
  3. Chernova V.M. Toxic liver lesions: modern views and approaches to therapy. Acute and emergency conditions in doctor’s practice. 2011; 2: 26-30 (in Russian).
  4. Reuben A., Koch D.G., Lee W.M. Drug-Induced Acute Liver Failure: Results of a U.S. Multicenter, Prospective Study. Hepatology. 2010; 52 (6): 2065-2076.
  5. Got’e S.V., Moysyuk Ya.G., Khomyakov S.M. Donorship and organ transplantation in the Russian Federation in 2014. VII Statement of the Register of the Russian Transplant Society. Bulletin of transplant and artificial organs. 2015; 17 (2): 7-22 (in Russian).
  6. Uryvaeva I.V. Stem cells in liver regeneration. In: Pal’tsev M.A., ed. Biology of stem cell and cell technologies. vol. 2. Moscow: Meditsina; 2009 (in Russian).
  7. Repin V.S., Sukhikh G.T. Medical cell biology. Moscow: Russian Academy of Medical Sciences: BEB & M.; 1998 (in Russian).
  8. Sukhikh G.T. Transplantation of fetal cells in medicine: present and future. Byull. Eksperim. Biol. Med. 1998; 126 (1): 3-13 (in Russian).
  9. Weiss T.S., Lichtenauer M., Kirchner S., Stock P., Aurich H., Christ B. et al. Hepatic progenitor cells from adult human livers for cell transplantation. Hepatology. 2008; 57: 1129-1138.
  10. Zhang H., Liu Z., Li R., Wang D., Liu W., Li J. et al. Transplantation of embryonic small hepatocytes induces regeneration of injured liver in adult rat. Transplantation Proceedings. 2009; 41 (9): 3887-3892.
  11. Lyundup A.V. Application of mesenchymal stromal marrow bone cells for correction of fibrosing liver damage. Cand. med. sci. diss. Moscow; 2011 (in Russian).
  12. Lee M.J., Jung J., Na K.H. et al. Anti-fibrotic effect of chorionic platederived mesenchymal stem cells isolated from human placenta in a rat model of CCl4-injured liver: potential application to the treatment of hepatic diseases. Cell Biochemistry. 2010; 111 (6): 1453-1463.
  13. Rambhatla L., Chiu C.P., Kundu P., Peng Y., Carpenter M.K. Generation of hepatocyte-like cells from human embryonic stem cells. Cell Transplantation. 2003; 12 (1): 1-11.
  14. Basma H., Soto-Gutiérrez A., Yannam G.R., Liu L., Ito R., Yamamoto T. et al. Differentiation and transplantation of human embryonic stem cell-derived hepatocytes. Gastroenterology. 2009; 136: 990-999.
  15. Merkulov G.A. Textbook on pathological and histological techniques. Moscow; Medicine; 1969 (in Russian).
  16. Freshney R.I. Culture of Animal Cells. In: A manual of Basic Techniques. New York: 1995; 39: 184-185.
  17. McGrath K., Koninski A., Malik J. et al. Circulation is established in a stepwise pattern in the mammalian embryo. Blood. 2003; 101: 1669-1672.
  18. Kumar G.L., Rudberk L. (ed. Frank G.A. and Malkov P.G.). Immunohistochemical methods: Guide. Moscow; 2011 (in Russian).
  19. Payushina O.V., Domaratskaya E.I., Starostin V.I. Cellular composition and regulatory functions of the stroma of the germinal liver. Cytology. 2012; 54 (5): 369-380 (in Russian).
  20. Faktor V.M., Engel’gardt N.V., Yazova A.K. et al. Common antigens of mouse oval cells and cholangiocytes: detection with monoclonal antibodies. Ontogenies. 1990; 21: 625-632 (in Russian).
  21. Petrakova O.S., Chernioglo E.S., Terskikh V.V., Kalistratova E.N., Vasil’ev A.V. The use of cellular technologies in the treatment of liver pathologies. Acta naturae. 2012; 3 (14): 18-33 (in Russian).

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Protasova G.A., Shabasheva L.V., Popov V.B.


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 81728 от 11 декабря 2013.