Therapeutic effect of mesenchymal stem cells in acute kidney injury: implication of inflammatory and oxidative stress pathways

Abstract

Acute kidney injury (AKI) is a multi-factorial and multi-system disorder which is clinically associated with a rapid loss of renal functions. It is described as one of the major contributors to mortality worldwide. Modern dialysis techniques and pharmacological therapy had no significant impact on overall mortalities caused by AKI. Hence, it becomes important to seek for other therapeutic interventions for AKI treatment. Stem cell replacement therapy has a great promise for AKI as it provides an approach for repairment of deteriorated organs and tissues. The main target of this research was to appraise the therapeutic outcome of bone marrow mesenchymal stem cells (BM-MSCs) and adipose-derived mesenchymal stem cells (AD- MSCs) against AKI in rat model. Adult male albino rats were equally randomized into nine groups: (1) Control, (2) Cisplatin, (3) Cisplatin+losartan, (4) Cisplatin+BM-MSCs (1x10 6 cells/rat), (5) Cisplatin+BM-MSCs (2x10 6 cells/rat), (6): Cisplatin+BM-MSCs (4x10 6 cells/rat), (7) Cisplatin+AD-MSCs (1x10 6 cells/rat), (8) Cisplatin+AD-MSCs (2x10 6 cells/rat) and (9) Cisplatin+AD-MSCs (4x10 6 cells/rat). The data showed significant enhancement in serum creatinine, urea, kidney injury molecule-1, tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-18, macrophage inflammatory protein-2 and malondialdehyde levels. While, significant inhibition of catalase and superoxide dismutase enzymes activity in serum of rats administrated cisplatin has been registered. On the contrary, MSCs transplantation could significantly recover renal functions, suppress the inflammatory markers, repress the oxidative stress marker and promote the anti-oxidative enzymes activity. The histopathological findings illustrated that MSCs have regenerative potentiality as manifested by minimizing the inflammatory cells infiltration and congested glomerular capillaries. Conclusively, MSCs therapy has a favorable impact in lessening kidney derangement after AKI through monitoring the inflammatory response and restoring oxidant/antioxidant homeostasis.