Pre-clinical evaluation of the effectiveness of the developed bioengineering means for therapy of lack of functions of the liver

S.V. Kostyukova 1, 2, A.V. Korotkov 1, 2, D.A. Sichkar 1, 2, E.A. Shuman 1, 2, M.A. Desyatova 1, O.G. Makeev 1, 2

 

1 Institute of Medical Cell Technologies, Yekaterinburg, Russian Federation;

2 Ural State Medical University, Yekaterinburg, Russian Federation

 

Abstract. The goal of the study is to obtain convincing data on the effectiveness of the use of multipotent mesenchymal stromal cells (MMSCs) transfected with a plasmid vector with the hepatocyte growth factor gene (HGF), as well as spheroids from MMSCs transfected with the same vector (SFMSC). Materials and methods. Morphological and morphometric studies were performed on Wistar rats (n=54) 30 and 90 days after transplantation of a suspension of transfected MMSCs and cell spheroids. The results obtained were statistically processed. Results. Positive changes of the studied parameters in the dynamics of observation are shown. Thus, therapy with the suspension of transfected MMSCs and SFMSCs by the number of binuclear cells and the thickness of connective tissue septa significantly differed from the corresponding indices in the control group.

 

Keywords: cirrhosis, multipotent mesenchymal stromal cells, transdifferentiation, gene therapy, hepatocyte growth factor

 

There is no conflict of interest.

Contact details of the corresponding author:

Oleg G. Makeev

larim@mail.ru

Received 26.11.2020

For citation:

Kostyukova S.V., Korotkov A.V., Sichkar D.A., Shuman E.A., Desyatova M.A., Makeev O.G. Pre-clinical evaluation of the effectiveness of the developed bioengineering means for therapy of lack of functions of the liver. Url: http://vestnikural.ru/article/1142 [Online] Vestn. Ural. Med. Akad. Nauki. = Journal of Ural Medical Academic Science. 2020, Vol. 17, no. 3, pp. 233–242. DOI: 10.22138/2500-0918-2020-17-3-233-242 (In Russ)

 

REFERENCE

  1.      Scaglione S., Kliethermes S., Cao G., Shoham D., Durazo R., Luke A., Volk M. L. et al. The epidemiology of cirrhosis in the United States. Journal of clinical gastroenterology. – 2015. – Vol. 49. – No. 8. – pp. 690-696.
  2.      Sakai Y, Takamura M, Seki A, et al. Phase I clinical study of liver regenerative therapy for cirrhosis by intrahepatic arterial infusion of freshly isolated autologous adipose tissue-derived stromal/stem (regenerative) cell. Regen Ther. 2017;6:52-64. Published 2017 Mar 9. doi:10.1016/j.reth.2016.12.001.
  3.      Mahmood A, Seetharaman R, Kshatriya P, Patel D, Srivastava AS. Stem Cell Transplant for Advanced Stage Liver Disorders: Current Scenario and Future Prospects [published online ahead of print, 2019 Oct 4]. Curr Med Chem. 2019;10.2174/0929867326666191004161802. doi:10.2174/0929867326666191004161802
  4.      Alt EU, Winnier G, Haenel A, et al. Towards a Comprehensive Understanding of UA-ADRCs (Uncultured, Autologous, Fresh, Unmodified, Adipose Derived Regenerative Cells, Isolated at Point of Care) in Regenerative Medicine. Cells. 2020;9(5):E1097. Published 2020 Apr 29. doi:10.3390/cells9051097
  5.      Cho K.A., Ju S.Y., Cho S.J., Jung Y.J., Woo S.Y., Seoh J.Y. 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 Biology International. – 2009. – Vol. 33. – No. 7. – pp. 772-777.
  6.      Parola M., Robino G. Oxidative stress-related molecules and liver fibrosis. Journal of hepatology. — 2001. — Vol. 35. — No. 2. — pp. 297-306.
  7.      Nahon P, Ganne-Carrié N. Management of patients with pre-therapeutic advanced liver fibrosis following HCV eradication. JHEP Rep. 2019;1(6):480-489. Published 2019 Nov 18. doi:10.1016/j.jhepr.2019.11.001.
  8.      Mesenchymal stem cells showed the highest potential for the regeneration of injured liver tissue compared with other subpopulations of the bone marrow. K. A. Cho [et al.] Cell. Biol. Int. 2009 Jul. Vol. 33, No. 7. pp. 772-777.
  9.      Zuk P.A., Zhu M., Ashjian P., De Ugarte D.A., Huang J.I., Mizuno H., Hedrick M.H. et al. Human adipose tissue is a source of multipotent stem cells. Molecular biology of the cell. — 2002. — Т. 13. – No. 12. — pp. 4279-4295.
  10.    Collan Y. Morphometry in pathology: another look at diagnostic histopathology. Pathol Res Pract. 1984;179(2):189 192. doi:10.1016/S0344-0338(84)80126-0
  11.    Kesten S, Fraser JK. Autologous Adipose Derived Regenerative Cells: A Platform for Therapeutic Applications. Surg Technol Int. 2016;29:38-44.
  12.    Lockhart RA, Aronowitz JA, Dos-Anjos Vilaboa S. Use of Freshly Isolated Human Adipose Stromal Cells for Clinical Applications. Aesthet Surg J. 2017;37(suppl_3):S4-S8. doi:10.1093/asj/sjw270

 

Authors

Artem V. Korotkov

Institute of Medical Cell Technologies

Ural State Medical University

Candidate of Medical Sciences, Leading Researcher

Russian Federation, 620026, Yekaterinburg, st. Karl Marx, 22 a

akorotkov64@mail.ru

 

Svetlana V. Kostyukova

Institute of Medical Cell Technologies

Ural State Medical University

Ph.D., Leading Researcher

Russian Federation, 620026, Yekaterinburg, st. Karl Marx, 22 a

svkostukova@mail.ru

 

Daria A. Sichkar

Institute of Medical Cell Technologies

Ural State Medical University

Junior researcher

Russian Federation, 620026, Yekaterinburg, st. Karl Marx, 22 a

Sichkar2017@yandex.ru

 

Evgeniy A. Shuman

Institute of Medical Cell Technologies

Ural State Medical University

Researcher

Russian Federation, 620026, Yekaterinburg, st. Karl Marx, 22 a

evgenyshuman@gmail.com

 

Maria A. Desyatova

Ural State Medical University

Junior Researcher

Russian Federation, 620109, Yekaterinburg, st. Klyuchevskaya, 17, of. 304/305

mardesyatova03@yandex.ru

 

Oleg G. Makeev

GAUZ SO IMKT, Yekaterinburg, Russia

FGBOU HE USMU Ministry of Health of Russia, Yekaterinburg, Russia

Doctor of Medical Sciences, Professor, Chief Researcher

620026, Yekaterinburg, st. Karl Marx, 22 a

larim@mail.ru

 
 
 

Authorization