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

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.

Curcumin-Induced Heme Oxygenase-1 Expression Prevents H2O2-Induced Cell Death in Wild Type and Heme Oxygenase-2 Knockout Adipose-Derived Mesenchymal Stem Cells

“…It has been shown that pre-conditioning of MSCs with melatonin [61], NO-donor S -nitroso N -acetylpenicillamine (SNAP) [64], or overexpression of transcription factor nuclear factor-erythroid 2-related factor 2 (nrf2) [18] can prevent MSC death caused by H 2 O 2 . Interestingly, these preconditioning factors are also potent inducers of HO-1 [65,66,67].…”

Stromal cell derived factor-1alpha protects stem cell derived insulin-producing cells from glucotoxicity under high glucose conditions in-vitro and ameliorates drug induced diabetes in rats

“…Futhur more, pre-conditioning of MSCs with growth factors etc. plays a major role in augmenting resistance of MSCs to stress due to injury or disease in vitro or in vivo [46]. …”

Mesenchymal Stem/Stromal Cells in Liver Fibrosis: Recent Findings, Old/New Caveats and Future Perspectives

“…Estrada et al [90] showed that MSCs cultured at low oxygen tension (3 %) are more genetically stable and grow faster than in normoxic conditions (20 % oxygen). By preconditioning rat BM-MSCs with S-nitroso N-acetyl penicillamine (SNAP), Masoud et al [91] were able to increase the survival and proliferation of MSCs, likely through the upregulation of key genes (such as IGF-I, AKT, BCL-1 and PCNA); nevertheless, whether or not this treatment might increase their migratory capacity remains to be elucidated. Finally, Ahmadbeigi et al [92] proposed to use, as source of MSCs, the cell aggregates which appear at the upper fraction after ficollpaque centrifugation or are left after filtering the suspension of extruded bone marrow samples.…”