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

Muhammad Shareef Masoud,Muhammad Zeeshan Afzal,Sheikh Riazuddin,Shaheen N Khan,Azra Mehmood,Sanam Saiqa Anwar

doi:10.1186/1479-5876-10-243

Abstract

BackgroundIschemia 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.MethodsMSCs 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.ResultsWe 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.ConclusionThe results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury.

Highlights

Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity
We report that S-nitroso N acetylpenicillamine (SNAP) pre-conditioning of Mesenchymal stem cells (MSCs) improved their potential against oxidative stress, enhanced their proliferation and reduced apoptosis in vitro
After SNAP pre-conditioning, cytotoxic effects of H2O2 were markedly decreased compared to non pre-conditioned control

Summary

Introduction

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. Inflammatory process and primary ischemic injury in vascular cells results in prolonged localized ischemia that substantially increases severity of injury in affected areas. MSCs are multi-potent cell population residing in bone marrow. These are capable of differentiating into cell types other than their tissue of origin. It has been reported that pre-conditioning of different tissues by a prior stimulus provides protection against injury [6]. The most extensively studied pre-conditioning stimulus is brief sub-injurious ischemia, which induces protection against subsequent ischemic injury [7]. Similar protective effects can be triggered by growth factors, cytokines or with some pharmacological agents [5,8]

Methods

Results

Discussion

Conclusion