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Stem Cells International
Volume 2016, Article ID 3585362, 12 pages
http://dx.doi.org/10.1155/2016/3585362
Research Article

Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin

1Department of Nephrology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
2Institute of Cell Biology, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia
3Institute of Pathology, Medical Experimental Centre, Faculty of Medicine, University of Ljubljana, Zaloška 4, 1000 Ljubljana, Slovenia
4National Institute of Biology, 1000 Ljubljana, Slovenia
5Jožef Štefan International Postgraduate School, 1000 Ljubljana, Slovenia
6Department of Rheumatology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia
7Lek Pharmaceuticals d.d. Ljubljana, 1000 Ljubljana, Slovenia
8Department of Experimental Oncology, Institute of Oncology, 1000 Ljubljana, Slovenia

Received 17 July 2015; Revised 11 October 2015; Accepted 21 October 2015

Academic Editor: Xiaoyang Zhao

Copyright © 2016 Željka Večerić-Haler et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG). We demonstrated that ATG pretreatment, when followed by MSC transplantation, significantly improved injured renal function parameters, as evidenced by decreased blood urea nitrogen and serum creatinine concentration, as well as improved renal morphology. This tissue restoration was also supported by increased survival of mice. The beneficial effects of ATG were associated with reduced level of inflammatory protein serum amyloid A3 and induced antioxidative expression of superoxide dismutase-1 (SOD-1), glutathione peroxidase (GPx), and hem oxygenase-1 (HO-1). Infused MSCs became localised predominantly in peritubular areas and acted to reduce renal cell death. In conclusion, these results show that ATG diminished in situ inflammation and oxidative stress associated with cisplatin-induced acute kidney injury, the effects that may provide more favourable microenvironment for MSC action, with consequential synergistic improvements in renal injury and animal survival as compared to MSC treatment alone.