Cell and Organ Transplantology. 2024; 12(2):118-125 (e2024122169).
DOI: 10.22494/cot.v12i2.169

Comparative effects of mesenchymal stromal cells of various origins and sources on biochemical parameters in the hippocampus of rats during cerebral ischemia-reperfusion

Konovalov S.¹, Moroz V.¹, Yoltukhivskyi M.¹, Gadzhula N.¹, Deryabina O.^2,3, Kordium V.^2,3

• 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
• ³Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine

Abstract

In neurodegenerative processes of the brain, the hippocampus is primarily affected, leading to subsequent cognitive impairments caused by increased generation of reactive oxygen and nitrogen species. These reactive species induce apoptosis and necrosis of neurons. Cell therapy using mesenchymal stromal cells (MSCs) has shown promising potential in activating endogenous mechanisms of neuroregeneration in response to ischemic injury of brain structures.
The purpose of this study is to investigate the therapeutic potential of MSCs from various origins, MSC lysate, and the reference drug citicoline on the energy component of neuronal metabolism, as well as oxidative and nitrosative stress in the rat hippocampus under conditions of cerebral ischemia-reperfusion (IR).
Material and methods. The experiment was conducted on 126 Wistar rats with a modeled pathology (20-minute IR of the internal carotid arteries). The animals were injected with human umbilical cord Wharton’s jelly-derived MSCs, human and rat adipose-derived MSCs, rat embryonic fibroblasts, MSC lysate, or citicoline immediately after the removal of the ligatures. Biochemical parameters of carbohydrate metabolism (glucose, lactate), oxidative (NADPH oxidase activity) and nitrosative stress (NO synthase activity) in the rat hippocampus were determined on days 7 and 14 after IR under the conditions of cerebral IR and on the background of its correction.
Results. It was established that during ischemia-reperfusion in the rat hippocampus, glucose and lactate levels increase, aerobic glucose oxidation is inhibited, anaerobic glycolysis intensifies, and lactic acidosis develops in hippocampal cells. Additionally, NADPH oxidase activity decreases, and an imbalance occurs in the nitric oxide system. A positive effect was observed from the transplantation of human umbilical cord Wharton’s jelly-derived MSCs and rat embryonic fibroblasts, as well as from the use of citicoline, in stabilizing glucose, lactate, NADPH oxidase, and nitric oxide levels. In contrast, the transplantation of human and rat adipose-derived MSCs was significantly less effective than citicoline and demonstrated no statistically significant modulatory effect on biochemical parameters in the hippocampus of experimental animals with IR.
Conclusions. Transplantation of human umbilical cord Wharton’s jelly-derived MSCs was not inferior to citicoline and, compared to other tested MSCs and their lysate, more effectively contributed to the recovery of disturbed energy processes (glucose levels) and the elimination of metabolic acidosis (lactate levels) in the hippocampus of rats. Moreover, it demonstrated a positive modulatory effect on the oxidant-antioxidant balance, as indicated by NADPH oxidase activity levels.

Keywords: mesenchymal stromal cells; hippocampus; cerebral ischemia-reperfusion injury; carbohydrate metabolism; oxidative stress

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