Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

Mekhno N.; Dovgalyuk A.; Korda M.; Yaremchuk O.

doi:10.22494/cot.v12i1.163

Cell and Organ Transplantology. 2024; 12(1):44-50
DOI: 10.22494/cot.v12i1.163

Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice

Mekhno N., Dovgalyuk A., Korda M., Yaremchuk O.

I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine

Abstract

Antiphospholipid syndrome is an autoimmune disease characterized by vascular thrombosis and/or obstetric pathology as well as the presence of antibodies against membrane phospholipids or certain phospholipid-related proteins.
Objective. The aim of the research is to study the effect of mesenchymal stem cells, nitric oxide modulators (L-arginine and aminoguanidine) on the level of cytokines in bronchoalveolar lavage in experimental antiphospholipid syndrome in mice.
Material and methods. Antiphospholipid syndrome was modeled on female BALB/c mice by intramuscular injections of cardiolipin 1.2 mg/kg 4 times with a 14-day interval. Cryopreserved human umbilical cord-derived mesenchymal stem cells (5×10⁶ cells/kg) were injected once intraperitoneally, L-arginine (25 mg/kg) and aminoguanidine (10 mg/kg) were administered intraperitoneally 1 time per day during 10 days after APS had developed. The cytokines concentration in bronchoalveolar lavage from the lungs was assessed by ELISA in 10 days after APS development.
Results. In the bronchoalveolar lavage of the BALB/c mice with experimental APS, an increased level of pro-inflammatory cytokines IL-1β, IL-6, TNF-α and decreased level of anti-inflammatory IL-4 and IL-10 were found. It was established that in cases of APS and administration of stem cells the concentration of proinflammatory cytokines decreased: IL-1β by 32.4 %, IL-6 by 30.6 % and TNF-α by 36.1 %, respectively, compared to the APS animals. At the same time the level of IL-4 increased by 50.5 % and IL-10 – by 57.5 % in the group of animals administered with stem cells compared to those with APS.
Conclusion. In cases of correction of modeled antiphospholipid syndrome in mice using mesenchymal stem cells and combined application of mesenchymal stem cells and nitric oxide modulators (L-arginine and aminoguanidine), a decrease in the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α ) and an increase in the level of anti-inflammatory cytokines (IL-4 and IL-10) in bronchoalveolar lavage has been established.

Keywords: antiphospholipid syndrome; interleukins; TNF-α; nitric oxide; mesenchymal stem cells; bronchoalveolar lavage

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How to cite

Mekhno N, Dovgalyuk A, Korda M, Yaremchuk O. Human umbilical cord-derived mesenchymal stem cells and nitric oxide modulators attenuate the proinflammatory cytokine pattern in experimental antiphospholipid syndrome in mice. Cell Organ Transpl. 2024; 12(1):44-50. Available from: https://doi.org/10.22494/cot.v12i1.163

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