The effects of combined administration of human umbilical cord-derived multipotent mesenchymal stromal cells and melatonin or fibroblast growth factor-2 to aged mice with a toxic cuprizone model of demyelination
Authors:   State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Labunets I. , Utko N. ,   State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Toporova O. ,   1State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine 2Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine, Pokholenko Ia. ,   1State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine 2Institute of Molecular Biology and Genetics of the National Academy of Sciences of Ukraine, Kyiv, Ukraine, Panteleymonova T. ,   State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Litoshenko Z. ,   State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine, Butenko G. ,   State Institute of Genetic and Regenerative Medicine of the National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
Published: July 2021

The effect of transplantation of umbilical cord-derived multipotent mesenchymal stromal cells (UC-MMSCs) to patients with demyelinating diseases depends on the age of the recipient and can change under the influence of hormones or growth factors. Purpose. To investigate the effect of exogenous melatonin and recombinant human fibroblast growth factor-2 (rhFGF-2) on the effects of UC-MMSCs transplanted into aged mice with an experimental model of multiple sclerosis. Material and methods. 129/Sv mice, 15-17 months old, received the neurotoxin cuprizone with food for 3 weeks. From the 10th day of the cuprizone diet, 5•105 UC-MMSCs were injected intravenously. From the 11th day they received melatonin at 600 p.m. or rhFGF-2. The behavioral parameters were evaluated in the open field test and rotarod test. In the brain, the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and the level of malondialdehyde (MDA) were assessed. Results. Cuprizone intake reduces the behavioral response in mice compared to the intact group. The transplantation of UC-MMSCs increases the number of rearings and muscle tone in mice. Melatonin injections enhance the effects of cells on these parameters, as well as increase the motor and emotional activity of animals. The injection of rhFGF-2 preserves the effect of cells on behavioral response and increases locomotor activity in mice. After the injection of UC-MMSCs with melatonin or rhFGF-2, the content of MDA in the brain decreases and the activity of antioxidant enzymes increases, this is more significant under the influence of melatonin. Conclusion. Exogenous melatonin and rhFGF-2 improve the effects of transplanted UC-MMSCs on behavioral responses and brain antioxidant defenses in aged mice with cuprizone diet. At the same time, the positive effect of the combination of cells with melatonin is more pronounced.