The effect of mesenchymal stromal cells of various origins on mortality and neurologic deficit in acute ischemia-reperfusion in rats

Konovalov, S.; Moroz, V. V.; Konovalova, N. A.; Deryabina, О. G.; Shuvalova, N. S.; Toporova, О. К.; Tochylovsky, A.; Кордюм, В. А.

doi:10.22494/cot.v9i2.132

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…Experimental animals were divided into 9 groups (Table 1). The obtaining of cells from human Wharton's jelly and adipose tissue, rat fetuses and adipose tissue, as well as cell lysate were described in our previous study [16].…”

Section: Methodsmentioning

confidence: 99%

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

Konovalov¹,

Мороз²,

Deryabina³

et al. 2022

COT

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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 7th and 14th 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.

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Section: Methodsmentioning

confidence: 99%

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

Konovalov¹,

Мороз²,

Deryabina³

et al. 2022

COT

Self Cite

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Comparative influence of mesenchymal stromal cells of different origin on DNA fragmentation of neuronal nuclei during ischemia-reperfusion of the somatosensory cortex of the rat brain

SV,

VM,

et al. 2023

ATROA

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Relevance: One of the main causes of stroke in acute cerebrovascular accident (ACVA) is ischemia, which begins with the formation of an acute neuronal energy deficit with subsequent activation of the "ischemic cascade" reactions that lead to irreversible damage to nervous tissue. Aim: To compare the effect of mesenchymal stromal cells (MSCs) of different origin and human MSCs from Wharton's jelly lysate on neuroapoptotic changes in the somatosensory cortex of the rat brain in conditions of model ischemia-reperfusion (IR) performed by ductal cytoflowmetry. Materials and methods: The experiment was carried out using 165 four-month-old male Wistar rats weighing 160-190 g, which were subjected to bilateral 20-minute transient ischemia-reperfusion (IR) of the internal carotid arteries. After modeling the pathology, the animals were injected into the femoral vein (iv) with MSCs obtained from umbilical cord Wharton jelly, human and rat adipose tissue in the amount of 106 cells/animal. Other groups of experimental animals were intravenously injected with fetal rat fibroblasts in the amount of 106 cells/animal (in 0.2 ml of physiological solution) and MSCs from umbilical cord Wharton's jelly lysate in a dose of 0.2 ml/animal. Control animals were injected intravenously with 0.2 ml of physiological solution. The level of DNA fragmentation in the nuclei of neurons of the somatosensory cortex of rats on the 7th day after ischemia-reperfusion was studied by flow cytometry. The research was carried out on a flow cytometer "Partech РАС" of the company Partech, Germany. The statistical significance of the differences was assessed by Student's t-test. Results: The study noted an increase in the level of fragmented DNA in a group of animals with IR by 3.25 times 7 days after model IR. The performed treatment showed that in groups with transplanted MSCs of various origins and MSC lysate from human Wharton's jelly cells, the intensity of DNA fragmentation in the nuclei of neurons in rat brain somatosensory cortex reliably decreased in1.8-2. 6 times compared with the group of control pathology (IR without treatment). Conclusions: Experimental 20-minute IR of the brain of rats forms a persistent focus of necrotic and apoptotic death of neurons, which is manifested by an increase in fragmented DNA (3.25 times). Intravenous transplantation of MSCs of various origin and lysate of MSCs from human Wharton jelly has a therapeutic effect in model IR, which is manifested by a decrease in the processes of neuro-destruction and neuroapoptosis in the area of ischemic brain damage Such effect is a link to the polytrophic mechanism of MSCs neuro-protective action.

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Comparative assessment of parameters of carbohydrate metabolism, oxidative and nitrosative stress in the somatosensory cortex and hippocampus of rats with cerebral ischemia-reperfusion and on the background of its correction

Konovalov,

Moroz,

Yoltukhivskyi

et al. 2024

Rep. of Vinnytsia Nation. Med. Univ.

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Annotation. Among the acute disorders of cerebral blood circulation, the most common is ischemic stroke, which leads to severe disability and mortality of working-age people. Cellular therapy using mesenchymal stromal cells (MSCs) aimed at endogenous neuroregeneration has become a promising direction in the therapy of ischemia-reperfusion injury of brain structures. The aim of the research is to study the effect of subtotal brain ischemia in rats followed by its reperfusion and correction on biochemical processes in the somatosensory cortex and hippocampus based on parameters of carbohydrate metabolism, oxidative and nitrosative stress. The experiment was carried out on 200 sexually mature Wistar rats with simulated ischemia-reperfusion of the internal carotid arteries, which were transplanted with MSCs derived from Wharton’s jelly of the human umbilical cord, MSCs derived from human and rat adipose tissues, rat embryonic fibroblasts, MSCs lysate and Citicoline. On the 7th and 14th days, parameters of carbohydrate metabolism, oxidative and nitrosative stress were determined in the somatosensory cortex and hippocampus of rats. Statistical analysis of the obtained data was performed using Statistica 6.0 (StatSoft® Snc, USA), parametric Student’s t-test and non-parametric Mann-Whitney U-test. It was established that ischemia-reperfusion injury was accompanied by an increase in glucose and lactate levels in the brain tissues of rats, inhibition of the process of aerobic glucose oxidation, an increase in anaerobic glycolysis, the development of lactic acidosis, a decrease in the level of NADPH oxidase activity, the development of nitrosative stress with more than two-fold activation of NO synthase and increased producing of nitrogen monoxide. More pronounced pathobiochemical changes were found in the hippocampus than in the somatosensory cortex of experimental animals. The best corrective effect on the level of biochemical parameters in the brain tissues had the reference drug Citicoline and human umbilical cord Wharton’s jelly-derived MSCs. Therapeutic intravenous transplantation of Wharton’s jelly-derived MSCs compared with other studied MSCs and MSCs lysate contributed to a better recovery of disturbed energy processes and eliminated metabolic acidosis and nitrosative stress in the hippocampus than in the somatosensory cortex of rats with brain ischemia-reperfusion. In the future, it is planned to create the most effective in neuroprotective properties an injectable medicine from class of MSCs for the treatment of patients with acute ischemic stroke.

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The effect of mesenchymal stromal cells of various origins on mortality and neurologic deficit in acute ischemia-reperfusion in rats

Cited by 3 publications

References 23 publications

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

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

Comparative influence of mesenchymal stromal cells of different origin on DNA fragmentation of neuronal nuclei during ischemia-reperfusion of the somatosensory cortex of the rat brain

Comparative assessment of parameters of carbohydrate metabolism, oxidative and nitrosative stress in the somatosensory cortex and hippocampus of rats with cerebral ischemia-reperfusion and on the background of its correction

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