Adipose-Derived Mesenchymal Stem Cells-Derived Exosomes Carry MicroRNA-671 to Alleviate Myocardial Infarction Through Inactivating the TGFBR2/Smad2 Axis.

Mesenchymal stem cells (MSCs) and their derived extracellular vesicles have been reported as promising tools for the management of heart disease. The aim of this study was to explore the function of adipose-derived MSCs (adMSCs)-derived exosomes (Exo) in the progression of myocardial infarction (MI) and the molecules involved. Mouse cardiomyocytes were treated with oxygen-glucose deprivation (OGD) to mimic an MI condition in vitro. The adMSCs-derived Exo were identified and administrated into the OGD-treated cardiomyocytes, and then the viability and apoptosis of cells, and the secretion of fibrosis- and inflammation-related cytokines in cells were determined. Differentially expressed microRNAs (miRNAs) in cells after Exo treatment were screened using a microarray analysis. The downstream molecules regulated by miR-671 were explored through bioinformatic analysis. Involvements of miR-671 and transforming growth factor beta receptor 2 (TGFBR2) in the exosome-mediated events were confirmed by rescue experiments. A murine model with MI was induced and treated with Exo for functional experiments in vivo. Compared to phosphate-buffered saline treatment, the Exo treatment significantly enhanced viability while reduced apoptosis of cardiomyocytes, and in reduced myocardial fibrosis and inflammation both in vitro and in vivo. miR-671 was significantly upregulated in cells after Exo treatment. Downregulation of miR-671 blocked the protective functions of Exo. miR-671 targeted TGFBR2 and suppressed phosphorylation of Smad2. Artificial downregulation of TGFBR2 enhanced viability of the OGD-treated cardiomyocytes. This study suggested that adMSC-derived exosomal miR-671 directly targets TGFBR2 and reduces Smad2 phosphorylation to alleviate MI-like symptoms both in vivo and in vitro.

Effects of eplerenone on cerebral aldosterone levels and brain lesions in spontaneously hypertensive rats.

Evidence indicates that renin-angiotensin-aldosterone system (RAS) inhibitors can protect the brain in Alzheimer's disease and Parkinson's disease. The current study evaluated the relationship between aldosterone and tissue damage in the brains of spontaneously hypertensive rats (SHRs) and whether the RAS inhibitor eplerenone can mitigate the damage seen in these rats. SHRs were randomly divided into eplerenone (n = 10) and SHR (n = 10) groups, and Wistar-Kyoto (WKY) rats (n = 10) were used as controls. Eplerenone 50 mg/kg/day was administered orally to the eplerenone group. Pathological changes to the hippocampal formation, plasma and encephalic aldosterone, and plasma potassium levels were compared among the groups. After 10 weeks, rats in the eplerenone and SHR groups showed higher systolic BP (p = .01) than the control group. Aldosterone levels in the brain were higher in the SHR group (0.20 ± 0.06 pg/ml) than in the eplerenone (0.14 ± 0.05 pg/ml, p = .044) or control (0.12 ± 0.07 pg/ml, p = .007) groups. Plasma aldosterone levels in the SHR group were 1.7 times higher than those in the control group (p = .006). Cerebral cortex was thinner in the SHR group (225.18 ± 15.43 µm) than in the eplerenone (240.38 ± 12.85 µm, p < .01) or control (244.72 ± 18.92 µm, p < .01) groups. Thickness did not differ between the latter two groups. The SHR group exhibited apoptotic cells in the hippocampal formation, which were rare in the eplerenone and control groups. Plasma potassium levels were higher in the eplerenone group than those in the other two groups (p < .05). Our results showed that eplerenone can alleviate brain damage (thinning of cortex and increased apoptosis) caused by aldosterone in a rat model of hypertension.

[Repair of spinal cord injury with rats' umbilical cord MSCs].

OBJECTIVE: To study the growth characteristics of umbilical cord MSCs (UCMSCs) in vitro and its effect on the nerve regeneration after spinal cord injury (SCI). METHODS: UCMSCs isolated from pregnant rats umbilical cord were cultured and purified in vitro. Sixty female Wistar rats weighing (300 +/- 10) g were randomized into three groups (n=20 per group). UCMSCs group (group A) in which UCMSCs suspension injection was conducted; DMEM control group (group B) in which 10% DMEM injection was conducted; sham group (group C) in which the animal received laminectomy only. Establish acute SCI model (T10) by Impactor model-II device in group A and group B. The recovery of the lower extremity was observed using BBB locomotor scoring system, neurofilament 200 (NF-200) immunofluorescence staining was performed to detect the neural regeneration, and then the corticospinal tract (CST) was observed using the biotinylated dextran amine (BDA) tracing. RESULTS: Cultured UCMSCs were spindle-shaped fibrocyte-like adherent growth, swirling or parallelly. The USMSCs expressed CD29, but not CD31, CD45, and HLA-DR. The BBB score was higher in group A than group B 4, 5, and 6 weeks after operation, and there was a significant difference between two groups (P < 0.05). The BBB scores at different time points were significantly lower in groups A and B than that in group C (P < 0.05). UCMSCs was proved to survive and assemble around the injured place by frozen section of the cords 6 weeks after injury. NF-200 positive response area in groups A, B, and C was (11,943 +/- 856), (7,986 +/- 627), and (13,117 +/- 945) pixels, respectively, suggesting there was a significant difference between groups A, C and group B (P < 0.05), and no significant difference was evident between group A and group C (P > 0.05). BDA anterograde tracing 10 weeks after operation demonstrated that more regenerated nerve fibers went through injured area in group A, but just quite few nerve fibers in group B went through the injuried cavity. The ratios of regenerative axons amount to T5 axons in group A and group B were smaller than that of group C (P < 0.05). CONCLUSION: UCMSCs can proliferate rapidly in vitro, survive and differentiate to neurons after being grafted into injured spinal cord. The transplantation of UCMSCs is effective in promoting functional recovery and axonal regeneration after SCI.