SOCS1 Regulates the Immunomodulatory Roles of MSCs on B Cells.

BACKGROUND AND OBJECTIVES: The effective use of MSCs for the treatment of some B cell-mediated immune diseases is quite limited. The main reason is that the immunomodulatory effects of mesenchymal stem cells (MSCs) on B cells are unclear, and their underlying mechanisms have not been fully explored. METHODS AND RESULTS: By co-culturing B cells with MSCs without (MSC/CTLsh) or with suppressor of cytokine signaling 1 (SOCS1) knockdown (MSC/SOCS1sh), we found that MSCs inhibited B cell proliferation, activation and terminal differentiation. Remarkably, the highest inhibition of B cell proliferation was observed in MSC/SOCS1sh co-culture. Besides, MSC/SOCS1sh reversed the inhibitory effect of MSCs in the last stage of B cell differentiation. However, MSC/SOCS1sh had no effect on inhibiting B cell activation by MSCs. We also showed that IgA+ B cell production was significantly higher in MSC/SOCS1sh than in MSC/CTLsh, although no difference was observed when both MSCs co-cultures were compared to isolated B cells. In addition, MSCs increased PGE2 production after TNF-α/IFN-γ stimulation, with the highest increase observed in MSC/SOCS1sh co-culture. CONCLUSIONS: Our results highlighted the role of SOCS1 as an important new mediator in the regulation of B cell function by MSCs. Therefore, these data may help to develop new treatments for B cell-mediated immune diseases.

Using semi-quantitative dynamic contrast-enhanced magnetic resonance imaging parameters to evaluate tumor hypoxia: a preclinical feasibility study in a maxillofacial VX2 rabbit model.

PURPOSE: To test the feasibility of semi-quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters for evaluating tumor hypoxia in a maxillofacial VX2 rabbit model. METHODS: Eight New Zealand rabbits were inoculated with VX2 cell solution to establish a maxillofacial VX2 rabbit model. DCE-MRI were carried out using a 1.5 Tesla scanner. Semi-quantitative DCE-MRI parameters, maximal enhancement ratio (MER) and slope of enhancement (SLE), were calculated and analyzed. The tumor samples from rabbits underwent hematoxylin-eosin (HE), pimonidazole (PIMO) and vascular endothelial growth factor (VEGF) immunohistochemistry (IHC) staining, and the PIMO area fraction and VEGF IHC score were calculated. Spearman's rank correlation analysis was used for statistical analysis. RESULTS: The MER values of eight VX2 tumors ranged from 1.132 to 1.773 (1.406 ± 0.258) and these values were negatively correlated with the corresponding PIMO area fraction (p = 0.0000002), but there was no significant correlation with the matched VEGF IHC score (p = 0.578). The SLE values of the eight VX2 tumors ranged from 0.0198 to 0.0532 s(-1) (0.030 ± 0.011 s(-1)). Correlation analysis showed that there was a positive correlation between SLE and the corresponding VEGF IHC score (p = 0.0149). However, no correlation was found between SLE and the matched PIMO area fraction (p = 0.662). The VEGF positive staining distribution predominantly overlapped with the PIMO adducts area, except for the area adjacent to the tumor blood vessel. CONCLUSIONS: The semi-quantitative parameters of DCE-MRI, MER and SLE allowed for reliable measurements of the tumor hypoxia, and could be used to noninvasively evaluate hypoxia during tumor treatment.

Expression of HGF/c-Met is dynamically regulated in the dorsal root ganglions and spinal cord of adult rats following sciatic nerve ligation.

Hepatocyte growth factor (HGF) and its receptor c-Met play pivotal roles in post-traumatic regeneration of the nervous system. However, following peripheral nerve injury, the role and regulation of the HGF/c-Met system is less clear. Therefore, using a sciatic nerve ligation (SNL) model, spatiotemporal changes in HGF and c-Met expression were detected in the dorsal root ganglions (DRGs) and lumbar spinal cords of adult rats. HGF expression following SNL was found to be significantly decreased in ipsilateral L4-L5 DRGs from day 3 to day 14, with the lowest levels of expression detected on days 5 and 7. In contrast, no significant change in HGF expression was detected in the lumbar spinal cords. c-Met expression in ipsilateral L4-L5 DRGs and within the ipsilateral dorsal horn was found to be significantly up-regulated following SNL, particularly from day 5 to day 14, with peak levels of expression detected on days 7 and 14. In contrast, c-Met levels following SNL consistently remained stable in the spinal ventral horn. These findings suggest that the HGF/c-Met system is spatiotemporally regulated by a unique pattern of signaling pathways induced by peripheral nerve injury, and these pathways have a role in promoting the survival of injured neurons, especially adult DRG sensory neurons.

[Spatial organization of neurons, astrocytes and vessels in rat brain].

OBJECTIVE: To demonstrate the spatial organization of neurons, astrocytes and vessels in rat brain. METHODS: Cerebral vascular was shown by vivi-perfusion with ink. Glial fibrillary acidic protein (GFAP) immunohistochemistry and nissl's staining were performed on the serial sections of frozen brain tissues. RESULTS: Astracytes distributed along the branches of blood vessels, and neurons in the region of the relatively rich blood vessels. Neurons and astrocytes presented regional distribution. CONCLUSION: This method can well indicate the spatial organization of neurovascular unit, the regional differences in the distribution may be related to physical activities and the corresponding adjustment function.