Tonsil-derived mesenchymal stem cells protect the kidney from gentamicin-induced acute kidney injury by incorporation into damaged renal tubules and amelioration of oxidative and endoplasmic reticulum stresses

Abstract

Background: Stem cell-based therapy is one of the tools for acute kidney injury (AKI) treatment. Tonsil tissue is a promising alternative source for the high-yield isolation of mesenchymal stem cells (MSCs). This study was undertaken to investigate the effects of tonsil-derived MSCs (T-MSCs) in animal model of AKI induced by gentamicin (GM). Methods: Twenty Sprague-Dawley rats were divided into four groups: Control, GM (70 mg/kg/day, intraperitoneal injection for 10 days), GM + T-MSCs (1 x 107 cells, intravenous injection at 1 day after the last vehicle/GM), and T-MSCs. Renal function, apoptosis, and markers of endoplasmic reticulum stress were measured on day 16 after the first vehicle/GM. Oxidative stress was assessed by measuring urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the expression of glutathione peroxidase (GPx) and catalase. Effects of T-MSCs on GM-induced apoptosis and oxidative stress in NRK cells were also evaluated using a co-culture technique of NRK cells and T-MSC. Results: In the GM + T-MSCs group, blood urea nitrogen, creatinine, and tubular damage score were lower compared to the GM group. T-MSCs injection decreased apoptotic cells and the expression of Bax, cytochrome c, and cleaved caspase and increased Bcl-2. T-MSC injection decreased urinary 8-OHdG and increased expression of GPx and catalase in the kidneys. Anti-human nuclei and PKH26 staining demonstrated the localization of T-MSCs in the tubules of renal cortex. In-vitro study revealed that T-MSCs or T-MSC-conditioned media ameliorated GM-induced nicotinamide adenine dinucleotide phosphate oxidase-1 expression, hydrogen peroxide generation, and apoptosis of NRK cells. Conclusion: Our study demonstrated that T-MSCs ameliorated GM-induced AKI by directly incorporating into the damaged renal tubules and exerting antiapoptotic and antioxidative effects.