Restoration of the nervous system in acute ischemia-reperfusion of the rat brain by intravenous administration of mesenchymal stromal cells of different origin

Abstract

Transplantation of mesenchymal stromal cells (MSCs) is a promising direction in the therapy of ischemic stroke, which promotes the regeneration of neurons in experimental and clinical studies. We evaluated the neuroprotective and angioprotective properties of intravenously transplanted allogeneic and xenogeneic MSCs obtained from human and rat adipose tissue, human umbilical cord Wharton jelly and its cells lysate compared with citicoline in a rat brain ischemia-reperfusion model. We studied the somatosensory cortex and CA1 zone of the hippocampus in rats using immunohistochemical analysis. It was found that the CA1 zone of the hippocampus was the most sensitive to ischemic damage. Analysis of brain sections 7 and 14 days after ischemia-reperfusion showed that all treatment options increased the staining intensity of NeuN-positive neurons, but did not reach the control value in sham-operated rats. To quantify the obtained results, we used the integrated fluorescence density indicator, which demonstrated a decrease in the fluorescence intensity of NeuN-positive neurons in 4.2 (7 days) and 3.2 times (14 days). All treatment variants significantly increased the intensity of fluorescence, but human umbilical cord Wharton’s jelly MSCs gave the best result. There was no difference in the fluorescence intensity of RECA-1-positive blood vessels. Thus, immunohistochemical analysis using a broad panel of antibodies against neurons and endothelial cells demonstrated that ischemia-reperfusion resulted in the death of NeuN-positive neurons in the CA1 zone of the hippocampus. Transplantation of stem cells of different origin, lysate of umbilical cord Wharton’s jelly MSCs and administration of citicoline had a neuroprotective effect on the CA1 zone of the hippocampus. However, the best result has been shown by the treatment with Wharton’s jelly MSCs.