Influence of mesenchymal stromal cells of different origins on behavioural reactions of rats with cerebral ischemia-reperfusion

Abstract

A new direction in cell therapy for ischemic stroke has been the use of mesenchymal stromal cells, which have shown a positive impact on functional changes in the central nervous system due to their neuroprotective effects, reduction of ischemia-reperfusion-induced injury, inhibition of ischemia-reperfusion-induced apoptosis, and restoration of motor function. This study aimed to investigate the effect of mesenchymal stromal cells of different origins, their lysate, and citicoline on the functional state of the central nervous system in rats with experimental brain ischemia-reperfusion. The study considered the effect of mesenchymal stromal cells derived from human umbilical cord Wharton’s jelly, human and rat adipose tissue, rat embryonic fibroblasts, as well as mesenchymal stromal cell lysate and citicoline on the emotional and behavioural responses of sexually mature Wistar rats (3-4 months) weighing 160-190 g. The behavioural responses of rats were studied using the open field test on the 7th and 14th days of the experiment; the following behavioural acts were recorded: ambulation (locomotion), climbing, rearing, and grooming. The significance of differences was determined using the non-parametric Mann-Whitney U test. It was established that after ischemia-reperfusion, animals with control pathology showed a significant decrease in the duration of episodes of ambulation in peripheral and central squares, vertical locomotor activity, and exploratory activity compared to the sham-operated group. In rats that received citicoline and transplanted human umbilical cord Wharton’s jelly mesenchymal stromal cells, a significant increase in the duration of episodes of horizontal locomotor activity was observed compared to other types of stem cells and the control. Intravenous administration of rat embryonic fibroblasts increased the emotional activity of the experimental animals. The least impact on locomotor and adaptive exploratory activity in rats with ischemia-reperfusion was registered in groups of animals that received mesenchymal stromal cells from human and rat adipose tissue, as well as mesenchymal stromal cell lysate. The practical significance of the study lies in the search for the most effective class of stem cells with neuroprotective properties for the creation of an injectable drug for intravenous transplantation in the treatment of patients with acute ischemic stroke