In the injured central nervous system (CNS), reactive astrocytes form a glial scar and are considered to be detrimental for axonal regeneration, but their function remains elusive. Here we show that reactive astrocytes have a crucial role in wound healing and functional recovery by using mice with a selective deletion of the protein signal transducer and activator of transcription 3 (Stat3) or the protein suppressor of cytokine signaling 3 (Socs3) under the control of the Nes promoter-enhancer (Nes-Stat3(-/-), Nes-Socs3(-/-)). Reactive astrocytes in Nes-Stat3(-/-) mice showed limited migration and resulted in markedly widespread infiltration of inflammatory cells, neural disruption and demyelination with severe motor deficits after contusive spinal cord injury (SCI). On the contrary, we observed rapid migration of reactive astrocytes to seclude inflammatory cells, enhanced contraction of lesion area and notable improvement in functional recovery in Nes-Socs3(-/-) mice. These results suggest that Stat3 is a key regulator of reactive astrocytes in the healing process after SCI, providing a potential target for intervention in the treatment of CNS injury.

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in a mouse spinal cord injury (SCI) model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT + serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPSderived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that preevaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.neural stem/progenitor cell | cell transplantation | regenerative medicine | remyelination | axonal regrowth

In pancreatic adenocarcinoma, the presence of CD4+ TILs together with CD8+ TILs serves as a good indicator of the patient's outcome after surgical treatment.

Although recent reports have described multipotent, self-renewing, neural crest-derived stem cells (NCSCs), the NCSCs in various adult rodent tissues have not been well characterized or compared. Here we identified NCSCs in the bone marrow (BM), dorsal root ganglia, and whisker pad and prospectively isolated them from adult transgenic mice encoding neural crest-specific P0-Cre/Floxed-EGFP and Wnt1-Cre/Floxed-EGFP. Cultured EGFP-positive cells formed neurosphere-like structures that expressed NCSC genes and could differentiate into neurons, glial cells, and myofibroblasts, but the frequency of the cell types was tissue source dependent. Interestingly, we observed NCSCs in the aorta-gonad-mesonephros region, circulating blood, and liver at the embryonic stage, suggesting that NCSCs migrate through the bloodstream to the BM and providing an explanation for how neural cells are generated from the BM. The identification of NCSCs in accessible adult tissue provides a new potential source for autologous cell therapy after nerve injury or disease.

No postoperative mortality and no positive ductal margins were achieved according to the above guidelines in a high-volume expert center. Long-term results, however, have not been significantly improved. A survival analysis of the patient series with homogeneous conditions derived from a short study period suggests the need for additional strategies including right hepatectomy for Bismuth type I or II tumors.

The purpose of this study was to clarify the relationship between the number of tumour-infiltrating T lymphocytes and the clinicopathological features and clinical outcome in patients with non-small-cell lung cancer (NSCLC). Tissue specimens from 109 patients who underwent surgical resection for NSCLC were immunohistochemically analysed for CD4 and CD8 expression. Patients were classified into two groups according to whether their tumours exhibited a 'high' or 'low' level of CD8 þ or CD4 þ lymphocyte infiltration. Although the level of infiltration by CD8 þ T cells alone had no prognostic significance, the survival rate for patients with both 'high' CD8 þ and 'high' CD4 þ T-cell infiltration was significantly higher than that for the other groups (log-rank test, P ¼ 0.006). Multivariate analysis indicated that concomitant high CD8 þ and high CD4 þ T-cell infiltration was an independent favourable prognostic factor (P ¼ 0.0092). In conclusion, the presence of high levels of both CD8 þ T cells and CD4 þ T cells is a significant indicator of a better prognosis for patients with NSCLC, and cooperation between these cell populations may allow a significantly more potent antitumour response than either population alone.

Neural stem/progenitor cells (NSPCs) hold promise in neural tissue replacement therapy after spinal cord injury. However, understanding the survival time of grafted NSPCs and determining the extent of migration away from transplantation sites are essential for optimizing treatment regimens. Here, we used in vivo bioluminescence imaging to noninvasively assess the survival and residence time of transplanted NSPCs at the injury sites in living animals, and we used histologic analyses to assess cell integration and morphology. Third-generation lentiviral vectors enabled efficient transduction and stable expression of both luciferase and a variant of green fluorescent protein in primary cultured NSPCs. Signals from these cells were detectable for up to 10 months or more after transplantation into the injured spinal cords of C57BL/6J mice. Histological and functional data supported the imaging data and suggest that the timing of NSPC transplantation may be a key determinant of the fates and function of integrated cells since cell survival and migration depended on the time of transplantation relative to injury. Optimization of cell therapies can be greatly accelerated and refined by imaging, and the methods in the present study can be widely applied to various research fields of regeneration medicine, including transplantation study.

Positron emission tomography (PET) with (18)F-2-deoxy-2-fluoro-D-glucose (FDG) has been investigated as a means of detecting certain primary tumors and their metastatic disease in recent years. The aim of this study was to compare the performance of FDG-PET and operative assessment with formal pathologic staging. Altogether, 85 patients had undergone surgical treatment for gastric cancer with curative intent, with FDG-PET preoperatively. The results using FDG-PET were compared with those using computed tomography (CT); they were also correlated with the pathologic findings. For quantitative analysis, the regional tumor uptake was measured by the standard uptake value (SUV) using a region of interest technique. Using FDG-PET, the primary tumor was visualized in 75.2% of patients. A comparison of the FDG uptake and the clinicopathologic findings showed that there was a significant association between FDG uptake and the depth of invasion, the size of the tumor, and lymph node metastasis. FDG-PET scans had less accuracy for diagnosing locoregional lymph nodes than CT because of a significant lack of sensitivity (23.3% vs. 65.0%). The survival rate for patients with high FDG uptake (SUV > 4) was significantly lower than that for those with low FDG uptake (SUV < 4) ( p < 0.05). FDG-PET was successful in detecting the primary gastric cancer lesion but not for finding early-stage gastric cancers. Detection of nodal metastasis also was not possible by FDG-PET. However, FDG-PET appears to provide important additional information concerning the aggressiveness of the tumor and the prognosis in patients with gastric cancer.