The effect of mesenchymal stromal cells of different origin on morphological parameters in the somatosensory cortex of rats with acute cerebral ischemia

Abstract

Ischemic stroke is the second leading cause of death and the leading cause of disability worldwide. So far, promising experimental data have been obtained regarding the elimination of neurological dysfunction and the reduction of the area of ischemic damage when using mesenchymal stromal cells (MSCs). Purpose: to characterize the influence of MSCs of different origin, MSC lysate of human Wharton cells and citicoline on the dynamics of destructive changes in the somatosensory cortex of rats with acute cerebrovascular accident according to light microscopy and micromorphometry data. Materials and methods. An experiment was performed using 190 -4-month-old male Wistar rats weighing 160-190 g, which were subjected to transient bilateral 20-minute ischemia-reperfusion (IR) of the internal carotid arteries. After modeling the pathology, the animals were injected into the femoral vein with obtained from human umbilical cord Wharton’s jelly-derived MSCs, human and rat adipose tissue-derived MSCs at a dose of 106 cells/animal. Other groups of experimental animals were intravenously injected with fetal rat fibroblasts at a dose of 106 cells/animal in 0.2 ml of physiological solution and lysate of human umbilical cord Wharton’s jelly-derived MSCs at a dose of 0.2 ml/animal. Control animals were injected IV with 0.2 ml of physiological solution. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. The studies were conducted on the 7th and 14th day. In the somatosensory cortex, the total number of neuron nuclei per 1 mm2 was counted, and the ratio of the number of intact neuron nuclei and nuclei with pathological changes (karyorrhexis and karyopyknosis) was also determined. Results: The transplantation of stem cells, lysate of human umbilical cord Wharton’s jelly-derived MSCs, or citicoline contributed to an increase in the number of neurons with nuclei in the somatosensory cortex, as well as an increase in the number of nuclei that did not undergo pathological changes. The transplantation of human umbilical cord Wharton’s jelly-derived MSCs had the most positive effect. The number of neuron nuclei in 1 mm2 that did not undergo pathological changes in the somatosensory cortex in this group of animals approached the number of nuclei in the group of pseudo-operated animals, while the number of nuclei that did not undergo pathological changes significantly exceeded the number of nuclei with signs of destruction. Conclusion: A significant increase in the number of neurons without signs of pathological changes was observed in all experimental groups of rats during the simulation of ischemic brain damage after the introduction of various types of studied mesenchymal stromal cells, lysate or citicoline. The most positive result in the somatosensory cortex was achieved after the introduction of human umbilical cord Wharton’s jelly-derived MSCs.