FIELD: medicine; pharmacology.
SUBSTANCE: group of inventions can be used to obtain and use medicines and biomaterials for neuroprotection and stimulation of brain tissue regeneration after injuries of various origins. A composition for neuroprotection and stimulation of brain neuroregeneration is proposed, the said composition is based on the components of the secretome of human mesenchymal stromal cells (MSCs) characterized by the presence of growth factors and cytokines in the culture medium including BDNF in an amount of at least 3 ng/ml, GDNF in an amount of at least 0.03 ng/l, VEGF in an amount of not less than 0.2 ng/ml, HGF in an amount of not less than 0.15 ng/ml, uPA in an amount of not less than 0.34 ng/ml and TGFb in an amount of not less than 0.055 ng/ml, besides the use of the indicated compositions as an agent for preventing glutamate-mediated death of neural cells, stimulating the polarization of cells of the monocyte-macrophage link in the anti-inflammatory direction (M2-phenotype), preventing the activation of microglial cells is proposed. The method of preparing the composition includes cultivating and conditioning primary human allogeneic MSCs isolated from adipose tissue for 2–5 passages in Dulbecco’s Modified Eagle Growth Medium (DMEM) with a glucose content of not more than 1 g/l without phenol red with the addition of penicillin/streptomycin, solutions of essential amino acids and vitamins, for 72–144 h, selection and purification of the culture medium from cell residues, concentration and purification of this medium to obtain a sterile concentrate. Also the following is proposed: an agent for neuroprotection and stimulation of neuroregeneration, including the specified composition in a therapeutically effective amount and auxiliary components, and a method of stimulating neuroprotection and regeneration of the brain after injury, including the introduction of the above composition or agent into the human body in a therapeutically effective amount.
EFFECT: reduction of neurological disorders severity within 14 days after modeling a stroke in experimental animals, and a decrease in the volume of brain damage by on average of 2 times according to MRI and histological examination compared with the control group (without composition), as well as a decrease in cell activation microglia to the basal level in the model of acute cerebrovascular accident by hemorrhagic type in the in vivo experiment.
24 cl, 17 dwg, 9 ex
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Authors
Dates
2023-09-12—Published
2022-05-23—Filed