Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment
1 National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan
2 Current Affiliation: Department of Bioinformatics and Biotechnology, Government College University, Faisalabad, 38000, Pakistan
3 College of Medicine- Pathology and Laboratory Medicine, University of Cicinnati Ohio, Albert Sabin way, Cicinnati, USA
4 Allama Iqbal Medical College/Jinnah Hospital Complex, University of Health Sciences, Lahore, Pakistan
5 The University of Lahore, 1Km Raiwind Road Lahore, Lahore, Pakistan
Journal of Translational Medicine 2012, 10:243 doi:10.1186/1479-5876-10-243Published: 5 December 2012
Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI.
MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM) or MB (1 μM) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted.
We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes’ expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase.
The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.