Mesenchymal stem cells versus their conditioned medium in the treatment of cisplatin-induced acute kidney injury: evaluation of efficacy and cellular side effects

Mesenchymal stem cells (MSCs) and their conditioned medium (CM) have been shown to ameliorate acute kidney injury (AKI). Potential risks of using stem cells are their participation in fibrosis and their differentiation to unwanted cells. The development of such adverse effects after therapy with CM is unknown. This study compares both the efficacy and safety of using MSCs or their CM in AKI model. Cisplatin was used to induce AKI in Sprague-Dawley rats. Rats were treated with either sub capsular injection of MSCs; or intraperitoneal injection of CM. Appropriate control was included and rats were sacrificed 5, 10, 30, and 60 days later. Kidney function parameters, urinary kidney injury molecule-1 (Kim-1), renal tissue damage, apoptosis, and proliferation were all determined. Special stains to detect adipocytes, osteoblasts, and fibrosis were also used. MSCs and their CM equally ameliorate kidney function deterioration, Kim-1 shedding in urine, renal tissue damage and tubular cell apoptosis. Even after 2 months, both equally reduced interstitial fibrosis. The MSC-treated group showed more enhancement of proliferation. However, adipocytes and osteoblast-like cells were detected where the stem cells were injected but not in the CM group. These results indicate that the use of CM might be an acceptable alternative to MSC therapy as it can attain comparable efficacy without the development of unwanted cells.