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

Journal of Translational Medicine

Research

Azra Mehmood¹  Sanam Saiqa Anwar¹  Shaheen N Khan¹  Sheikh Riazuddin²  Muhammad Zeeshan Afzal³  Muhammad Shareef Masoud⁴ 

[1]National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

[2]National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

[3]Allama Iqbal Medical College/Jinnah Hospital Complex, University of Health Sciences, Lahore, Pakistan

[4]The University of Lahore, 1Km Raiwind Road Lahore, Lahore, Pakistan

[5]National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

[6]College of Medicine- Pathology and Laboratory Medicine, University of Cicinnati Ohio, Albert Sabin way, Cicinnati, USA

[7]National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan

[8]Current Affiliation: Department of Bioinformatics and Biotechnology, Government College University, 38000, Faisalabad, Pakistan

关键词: MSCs;    SNAP;    Pre-conditioning;    Renal ischemia;    Cytoprotective factors;   

DOI  :  10.1186/1479-5876-10-243

 received in 2012-09-14, accepted in 2012-11-28,  发布年份 2012

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Masoud et al.; licensee BioMed Central Ltd. 2012