Abstract
We investigated changes in PA levels by the treatment of human bone-marrow-derived mesenchymal stem cells (hBM-MSCs) in ischemic stroke in rat brain model and in cultured neuronal SH-SY5Y cells exposed to oxygen-glucose deprivation (OGD). In ischemic rat model, transient middle cerebral artery occlusion (MCAo) was performed for 2 h, followed by intravenous transplantation of hBM-MSCs or phosphate-buffered saline (PBS) the day following MCAo. Metabolic profiling analysis of PAs was examined in brains from three groups: control rats, PBS-treated MCAo rats (MCAo), and hBM-MSCs-treated MCAo rats (MCAo + hBM-MSCs). In ischemic cell model, SH-SY5Y cells were exposed to OGD for 24 h, treated with hBM-MSCs (OGD + hBM-MSCs) prior to continued aerobic incubation, and then samples were collected after coculture for 72 h. In the in vivo MCAo ischemic model, levels of some PAs in brain samples of the MCAo and MCAo + hBM-MSCs groups were significantly different from those of the control group. In particular, putrescine, cadaverine, and spermidine in brain tissues of the MCAo + hBM-MSCs group were significantly reduced in comparison to those in the MCAo group. In the in vitro OGD system, N 1-acetylspermidine, spermidine, N 1-acetylspermine, and spermine in cells of the OGD + hBM-MSCs group were significantly reduced compared to those of OGD group.
Highlights
Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are regarded as promising agents in ischemic stroke therapy [1,2,3,4] because of their differentiation plasticity, easy attainability, and weak immune response inducing ability [5,6,7,8]
Outcomes from present experiments may provide new insight into our understanding of the complexity of biochemical and physiological events that occur in ischemic brain injury and after human bonemarrow-derived mesenchymal stem cell (hBM-MSC) replacement therapy in treatment for the stroke and other related disorders
The ischemic region was identified by DAPI and hBM-MSCs labelled with nuclei matrix antigen (NuMA) were found in the margin (about 3–5% of 1 × 106 hBM-MSCs, Figure 1(b)); these results are consistent with a previous report in the same model [27, 28]
Summary
Bone-marrow-derived mesenchymal stem cells (BM-MSCs) are regarded as promising agents in ischemic stroke therapy [1,2,3,4] because of their differentiation plasticity, easy attainability, and weak immune response inducing ability [5,6,7,8]. Autologous human bonemarrow-derived mesenchymal stem cell (hBM-MSC) transplantation in patients with ischemic stroke suggested hBMMSC’s potential for providing functional recovery [13]. This study suggests that autologous hBM-MSC transplantation may be a safe treatment method for ischemic stroke, the precise underlying therapeutic mechanisms of. Stem Cells International hBM-MSC transplantation remain unknown. Among the diverse biogenic compounds with low-molecular weights occurring in metabolic pathways, polyamines (PAs) serve as the most important biochemical indicator for various pathological conditions [14,15,16]. The precise characterization and the explicit role of PAs in brain ischemic conditions remain unknown
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