Open Access Research

Pre-conditioned mesenchymal stem cells ameliorate renal ischemic injury in rats by augmented survival and engraftment

Muhammad Shareef Masoud12*, Sanam Saiqa Anwar1, Muhammad Zeeshan Afzal13, Azra Mehmood1, Shaheen N Khan1 and Sheikh Riazuddin145

Author Affiliations

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

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Journal of Translational Medicine 2012, 10:243  doi:10.1186/1479-5876-10-243

Published: 5 December 2012

Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Keywords:
MSCs; SNAP; Pre-conditioning; Renal ischemia; Cytoprotective factors