Biology (May 2023)

Human Mesenchymal Stem Cells Modified with the NS5A Gene of Hepatitis C Virus Induce a Cellular Immune Response Exceeding the Response to DNA Immunization with This Gene

  • Olga V. Masalova,
  • Ekaterina I. Lesnova,
  • Vladimir A. Kalsin,
  • Regina R. Klimova,
  • Natalya E. Fedorova,
  • Vyacheslav V. Kozlov,
  • Natalya A. Demidova,
  • Kirill I. Yurlov,
  • Mikhail A. Konoplyannikov,
  • Tatyana N. Nikolaeva,
  • Alexander V. Pronin,
  • Vladimir P. Baklaushev,
  • Alla A. Kushch

DOI
https://doi.org/10.3390/biology12060792
Journal volume & issue
Vol. 12, no. 6
p. 792

Abstract

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Hepatitis C virus (HCV) is one of the basic culprits behind chronic liver disease, which may result in cirrhosis and hepatocarcinoma. In spite of the extensive research conducted, a vaccine against HCV has not been yet created. We have obtained human mesenchymal stem cells (hMSCs) and used them for expressing the HCV NS5A protein as a model vaccination platform. Sixteen hMSC lines of a different origin were transfected with the pcNS5A-GFP plasmid to obtain genetically modified MSCs (mMSCs). The highest efficiency was obtained by the transfection of dental pulp MSCs. C57BL/6 mice were immunized intravenously with mMSCs, and the immune response was compared with the response to the pcNS5A-GFP plasmid, which was injected intramuscularly. It was shown that the antigen-specific lymphocyte proliferation and the number of IFN-γ-synthesizing cells were two to three times higher after the mMSC immunization compared to the DNA immunization. In addition, mMSCs induced more CD4+ memory T cells and an increase in the CD4+/CD8+ ratio. The results suggest that the immunostimulatory effect of mMSCs is associated with the switch of MSCs to the pro-inflammatory phenotype and a decrease in the proportion of myeloid derived suppressor cells. Thus, the possibility of using human mMSCs for the creation of a vaccine against HCV has been shown for the first time.

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