The potential therapeutic effect of adipose-derived mesenchymal stem cells in the treatment of cutaneous leishmaniasis caused by L. major in BALB/c mice

Exp Parasitol. 2021 Mar:222:108063. doi: 10.1016/j.exppara.2020.108063. Epub 2021 Jan 4.

Abstract

Leishmaniasis is one of the most neglected tropical infectious diseases in the world. The emergence of drug resistance and toxicity and the high cost of the available drugs with a lack of new anti-leishmanial drugs highlight the need to search for newer therapies with anti-leishmanial activities. Due to the mesenchymal stem cell (MSC) immunomodulatory capacity, they have been applied in a wide variety of disorders. In this study, the potential effects of adipose-derived MSC (AD-MSCs) therapy and its combination with glucantime were evaluated in a murine model of cutaneous leishmaniasis induced by L. major. The results showed that AD-MSCs improved wound healing and decreased parasite burden. The real-time PCR results obtained from mice treated with AD-MSCs showed that IL-12 and TNF-α genes were upregulated. IL-10, arginase, and FOXP3 genes were downregulated whereas no differences in expression of the IL-4 gene were found. Overall, it seems that AD-MSCs therapy enhances Th1 immune response in L. major infected BALB/c mice. Unexpectedly, our results showed that the association of glucantime to AD-MSCs treatments did not lead to an increment in the anti-leishmanial activity.

Keywords: Adipose-derived mesenchymal stem cells; BALB/c mice; Cutaneous leishmaniasis; Cytokines; Leishmania major; Th1 response.

MeSH terms

  • Analysis of Variance
  • Animals
  • Arginase / genetics
  • Arginase / metabolism
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism
  • Gene Expression
  • Interleukin-10 / genetics
  • Interleukin-10 / metabolism
  • Interleukin-12 / genetics
  • Interleukin-12 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Leishmania major*
  • Leishmaniasis, Cutaneous / therapy*
  • Mesenchymal Stem Cells / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Th1 Cells / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Up-Regulation

Substances

  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Interleukin-12
  • Interleukin-4
  • Arginase