Cell and Organ Transplantology. 2022; 10(2):in press.
DOI: 10.22494/cot.v10i2.144

The effect of mesenchymal stromal cells of various origins on morphology of hippocampal CA1 area of rats with acute cerebral ischemia

Konovalov S.¹, Moroz V.¹, Deryabina O.², Klymenko P.^2,3, Tochylovsky A.⁴, Kordium V.^2,5

• ¹National Pirogov Memorial Medical University, Vinnytsya, Ukraine
• ²Institute of Genetic and Regenerative Medicine, M. D. Strazhesko National Scientific Center of Cardiology, Clinical and Regenerative Medicine, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine Kyiv, Ukraine
• ³D. F. Chebotarev State Institute of Gerontology, National Academy of Medical Sciences of Ukraine, Kyiv, Ukraine
• ⁴BioTexCom LLC, Kyiv, Ukraine
• ⁵Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Abstract

Every year, about 150,000 strokes occur in Ukraine, and more than 100,000 people die from the consequences of stroke and other circulatory disorders in the brain. So far, promising experimental data on the treatment of neurological dysfunction using mesenchymal stromal cells (MSCs) have been obtained.
Purpose: to characterize the impact of MSCs of various origins, lysate of Wharton’s jelly-derived MSCs and citicoline on the dynamics of destructive changes in the hippocampal CA1 area of rats with model of acute cerebral ischemia according to morphometric data.
Materials and methods. An experiment was performed using 4-month-old male Wistar rats, which were subjected to transient bilateral 20-minute ischemia-reperfusion (IR) of the internal carotid arteries. After modeling, the animals were injected intravenously with Wharton’s jelly-derived MSCs, human and rat adipose-derived MSCs at a dose 10⁶ cells/animal. Other groups were intravenously injected with rat fetal fibroblasts at a dose of 10⁶ cells/animal and lysate from Wharton’s umbilical cord MSCs at a dose of 0.2 mL/animal. Control animals were injected with 0.2 mL of saline. The last group of rats received a single dose of the reference drug citicoline at a dose of 250 mg/kg. On the 7^th and 14^th day, the total number of neuron nuclei per 1 mm² brain section was counted in the hippocampal CA1 area, and the ratio of the number of intact neuron nuclei and nuclei with changes (karyorrhexis and karyopyknosis) was determined.
Results. The transplantation of MSCs, lysate of Wharton’s jelly-derived MSCs, or citicoline contributed to a greater value of the number of nuclei in the hippocampal CA1 area, and the number of nuclei that did not undergo pathological changes also increased. The transplantation of Wharton’s jelly-derived MSCs had the most positive effect. The number of neuron nuclei per 1 mm² in the hippocampal CA1 area in this group of animals approached the number of nuclei in the group of sham-operated animals. At the same time, 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 modeling of ischemic brain injury after the administration of various types of studied mesenchymal stromal cells, lysate or citicoline. The most positive result in the hippocampal CA1 area was achieved after the administration of Wharton’s jelly-derived MSCs.

Key words: ischemic stroke; mesenchymal stromal cells; hippocampal CA1 area; cell transplantation


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