Experimental application of xenogenic fractionated proteomic secretome of stem and progenitor cells in acute ischemic kidney injury
Authors:   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation, Kirpatovskiy V.I. ,   Moscow, Russia, Sivkov A.V. ,   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia, Efremov G.D. ,   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia, Samoilova S.I. ,   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia, Frolova E.V. ,   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia, Apolikhin O.I. ,   N.A. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – Branch of the National Medical Research Centre of Radiology of the Ministry of Health of Russian Federation; Moscow, Russia
Published: April 2022

Introduction. Currently, the possibilities of cell therapy using stem cells for the correction of functional disorders of organs, including kidneys, are being widely investigated. The main mechanism of action of stem cells is considered to be the activation of cellular regeneration and the inhibition of apoptosis by the products of their secretion (secretome), which makes it necessary to study the mechanisms of action of the stem cells secretome. Aim of study. To study the relationship of the nephroprotective effect of the drug, which is a protein-peptide secretom of embryonic brain cells (SESC), with its effect on the regeneration of kidney cells damaged by ischemia and the activity of their apoptosis. Material and methods. Experiments were carried out on 40 mongrel male rats weighing 280-320 g. Acute kidney injury of varying severity was caused by removal of the right kidney and ischemia of the remaining left kidney for 60 minutes or 90 minutes (20 rats per group). In each of these groups, 10 rats were injected daily subcutaneously with SESC at a dose of 0.1 ml/kg (10 injections), and the other 10 rats were not treated. After 3, 7 and 14 days, the ischemic kidney was removed and subjected to histological examination and histochemical determination of the expression of the proliferation marker Ki-67 and the anti-apoptotic protein Bcl-2 in the kidney structures. Results. In the treatment of SESC, up to 20% of hypertrophied renal glomeruli were detected already on the 3rd day in the absence of glomeruli with glomerulosclerosis, whereas in control experiments at this time hypertrophied glomeruli were not detected, and the proportion of glomeruli with signs of glomerulosclerosis was 5-10%. On the 7th and 14th days in both groups, the proportion of hypertrophied glomeruli increased, being compared in the group with 60-minute ischemia, but maintaining higher values in experiments with 90-minute ischemia and SESC therapy compared with the control. Glomeruli with glomerulosclerosis were significantly less frequently detected in the treatment of SESC, regardless of the severity of ischemic damage. At the same time, the expression of Bcl-2 in renal glomerular cells during SESC therapy decreased significantly to a lesser extent than in control experiments, confirming the relationship of inhibition of apoptosis during SESC therapy with inhibition of the development of sclerotic processes. A significant increase in the number of epithelial cells expressing the proliferation marker Ki-67 on the 3rd day, followed by a gradual decrease in their number, was detected in the renal tubules during SESC therapy, whereas in the control an increase in the number of labeled cells occurred only on the 7th and 14th days. With an increase in the severity of ischemic damage, the proliferation-stimulating effect of SESC was prolonged up to 14 days. The proliferative effect of SESC therapy was accompanied by a decrease in damage to the renal tubules, and the percentage of tubules with necrotic epithelium progressively decreased from 3-5% to 0-1% with an increase in the period after the start of therapy (7 and 14 days), indicating epithelial regeneration, while in the control their proportion remained at a higher level. Conclusion. Stimulation of cell proliferation and inhibition of apoptosis of damaged cells play an essential role in the nephroprotective effect of SESC, as in stem cells.