INFLUENCE OF BONE MARROW ALLOGENEIC MULTIPOTENT MESENCHYMAL STROMAL CELLS ON THE FORMATION OF ANTI-ISCHEMIC KIDNEY PROTECTION

Abstract

Аim of this work was to study the influence of intravenous injection times of bone marrow allogeneic multipotent mesenchymal stromal cells (BM MMSCs) on kidney function and morphology in modeled ischemicreperfusion injury of kidney (IRIK). Materials and methods. The study was conducted on 90 male Wistar rats. On the original IRI model of a single kidney (60 min, warm ischemia) 4 groups of experiments were performed: in the first group the dose of 5 × 106 of BM MMSCs was administered intravenously 14 days before IRIK modeling; in the second group, the same dose of BM MMSCs was administered 7 days before IRIK; in the third group, the same dose of BM MMSCs was administered during kidney reperfusion after IRIK modeling; the fourth group served as the control group (IRIK without BM МMSCs). The study duration was 21 days since the start of IRIK modeling. In all groups the nitrogen secretory function of kidneys was examined and the histological condition of kidneys during the entire recovery period was evaluated. Besides, blood of rats of the first and the fourth groups was examined for proand anti-inflammatory cytokine levels and phagocytosis indices using the suspension of inactivated St. aureus. The significance of differences in these two groups was evaluated by Student's test at p < 0.05. Results. It has been demonstrated that the pretreatment with BM MMSCs (1 and 2 weeks before IRIK modeling) increased the anti-ischemic resistance of kidney while the administration of BM MMSCs on the day of IRIK modeling (during reperfusion) enhanced kidney damage, characterized by increased mortality, elevated levels of urea and creatinine in blood and structural injury of renal tissue, as compared to other groups. The comparative analysis of the first and fourth groups shows that BM MMSCs decrease the levels of pro-inflammatory cytokines and increase the levels of anti-inflammatory cytokines, as well as enhance potential of antimicrobial protection. Conclusion. Intravenous injection of BM MMSCs 1–2 weeks prior to IRIK modeling increases the kidney resistance to ischemia, reduces the severity of the systemic inflammatory response as well as the risk of infectious complications. However, considering the possibility of the summation of the injuring influence of ischemia and the stress of the adapting doses of BM MMSCs on ischemic kidney tissue during reperfusion, the search for the optimal concentrations of BM MMSCs needs to be continued.

Keywords

• kidney
• induction therapy
• mmscs
• bone marrow
• ischemic-reperfusion injury
• experimental model
• transplantation