The Role of Mesenchymal Stem Cells versus Its Conditioned Medium on Cisplatin Induced Renal Injury in Adult Albino Rat

Abstract

Cisplatin is a chemotherapeutic drug used in treatment of many organs cancers including those of head, neck, lung, testis, ovary and breast. Cisplatin nephrotoxicity is a major cause of AKI in about one third of patients under cisplatin treatment, so it is important to find a new effective treatment for cisplatin induced AKI. Stem cells have emerged as a promising way in the therapy of acute renal injury. Mesenchymal stem cells can be isolated from a variety of tissues including bone marrow. Most of previous studies suggested that bone marrow-derived mesenchymal stem cells (BMSCs) can protect against acute renal injury. Interestingly, the conditioned medium (CM) of stem cells has been found to minimize cisplatin-induced renal injury and improved both renal function and structure in some previous studies. The current study was undertaken to evaluate the capability of bone marrow derived mesenchymal stem cells (BMSCs) versus its conditioned medium (CM) in minimizing the cisplatin induced acute renal injury. Sixty adult female albino rats of average weight of 150 gm were used in the current study. The sixty adult females were divided into four groups: • Group I (Control group): consisted of 20 rats and was further subdivided into two subgroups. - Subgroup IA: consisted of 10 rats which, were given single intraperitoneal injection of 0.9 % physiological saline. - Subgroup IB: consisted of 10 rats which were given a single dose of phosphate buffered saline (PBS) in to tail vein. The animals of group I were sacrificed three days after injection. • Group II (cisplatin treated group): consisted of 20 rats that, were subdivided in to two subgroups: - Subgroup IIA: consisted of 10 rats which were given single intraperitoneal injection of cisplatin at a dose of 10mg/kg. The animals of this subgroup were sacrificed after one day of cisplatin injection. - Subgroup IIB: consisted of 10 rats which, were given cisplatin at the same dose and route as subgroup IIA. The animals of this subgroup were sacrificed after three days (4th day) of cisplatin injection. • Group III (stem cell treated group): consisted of 10 rats which were given cisplatin at the same dose and route as group II. Then, they were also treated with BMSCs injection at dose of 2x106 cells / rat in the tail vein one day after cisplatin injection. The animals of this group were sacrificed after three days of cisplatin injection. • Group IV (conditioned medium treated group): consisted of 10 rats which were given cisplatin at the same dose and route as group II. Then, they were injected with the conditioned medium (CM) at dose of 0.5 ml into tail vein one day after cisplatin injection. The animals of this group were sacrificed after three days of cisplatin injection. All animals were sacrificed after anesthesia with ether inhalation. Kidney specimens were prepared for different histological and immuno-histochemical stains. Morpho-metrical measurements and statistical analysis were performed. The results of this study revealed various degrees of apoptosis and necrosis in renal tubules of animals of group II. Sloughing of epithelial lining of some renal tubules to the lumen with formation of hyaline cast were detected. Loss of brush border of most of proximal tubules was observed. Fibrous tissue could be detected around renal tubules and in their lumens. Injection of BMSCs resulted in improvement of renal structure in group III. However injection of CM in group IV was less effective than BMSCs in improvement of renal injury. It was concluded that BMSCs injection resulted in marked improvement of renal structure more than CM in AKI.