BackgroundHepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and has poor prognosis. Specially, patients with HCC usually have poor tolerance of systemic chemotherapy, because HCCs develop from chronically damaged tissue that contains considerable inflammation, fibrosis, and cirrhosis. Since HCC exhibits highly heterogeneous molecular characteristics, a proper in vitro system is required for the study of HCC pathogenesis. To this end, we have established two new hepatitis B virus (HBV) DNA-secreting HCC cell lines from infected patients.MethodsBased on these two new HCC cell lines, we have developed chemosensitivity assays for patient-derived multicellular tumor spheroids (MCTSs) in order to select optimized anti-cancer drugs to provide more informative data for clinical drug application. To monitor the effect of the interaction of cancer cells and stromal cells in MCTS, we used a 3D co-culture model with patient-derived HCC cells and stromal cells from human hepatic stellate cells, human fibroblasts, and human umbilical vein endothelial cells to facilitate screening for optimized cancer therapy.ResultsTo validate our system, we performed a comparison of chemosensitivity of the three culture systems, which are monolayer culture system, tumor spheroids, and MCTSs of patient-derived cells, to sorafenib, 5-fluorouracil, and cisplatin, as these compounds are typically standard therapy for advanced HCC in South Korea.ConclusionIn summary, these findings suggest that the MCTS culture system is the best methodology for screening for optimized treatment for each patients with HCC, because tumor spheroids not only mirror the 3D cellular context of the tumors but also exhibit therapeutically relevant pathophysiological gradients and heterogeneity of in vivo tumors.Electronic supplementary materialThe online version of this article (10.1186/s13046-018-0752-0) contains supplementary material, which is available to authorized users.

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The physiologic function of natural killer T (NKT) cells in adaptive immunity remains largely unknown because most studies have used NKT cell agonists. In the present study, the role of NKT cells during the secondary effector phase was investigated separately from the primary immunization phase via adoptive transfer of differentiated effector T cells into naive recipients. We found that secondary antitumor CD8 + T-cell responses were optimal when NKT cells were present. Tumor-specific CD8 + effector T cells responded less strongly to tumor cell challenge in NKT cell-deficient recipients than in recipients with intact NKT cells. NKT cell-mediated enhancement of the secondary antitumor CD8 + T-cell response was concurrent with increased number and activity of tumorspecific CD8 + T cells. These findings provide the first demonstration of a direct role for NKT cells in the regulation of antigen-specific secondary T-cell responses without the use of exogenous NKT cell agonists such as A-galactosylceramide (A-GalCer). Furthermore, forced activation of NKT cells with A-GalCer during the secondary immune response in suboptimally immunized animals enhanced otherwise poor tumor rejection responses. Taken together, our findings strongly emphasize the importance of NKT cells in secondary CD8+ T-cell immune responses. [Cancer Res 2009;69(10):4301-8]

A bioinspired boron nitride nanosheet (BNNS)/gelatin nanocomposite consisting of hierarchically aligned layered BNNSs bonded with gelatin is fabricated by using electrostatic interactions between the oppositely charged functional groups on gelatin and the BNNSs. To enhance the self‐assembly and interfacial bond strength between these entities, the BNNSs are functionalized using hyperbranched polyglycerol. The 2D alignment of the BNNSs can be controlled by increasing the amount of BNNSs, or by a functionalization process, both of which result in transformation of the nanoscale structure from a randomly oriented to a brick‐and‐mortar structure. The mechanical properties of the resulting nanocomposite material, including the strength and modulus, are controlled by changing the composition of BNNSs and gelatin in the nanocomposite and by modifying the degree of alignment of the BNNSs in the material. This tuning of the mechanical properties yields a material whose performance resembles that of human cortical bone. In vitro cell viability experiments on the BNNSs/gelatin nanocomposite reveal that this artificial nacre supports adhesion, viability, and proliferation of adipose‐derived stem cells, all of which are essential for biomedical applications. Mechanical and biological testing of the material suggests applications of artificial nacre in biomedical fields and for tissue regeneration.

Background: The authors investigated the synergistic effects of adipose-derived stem cells and fat graft on skin wrinkles in a nude mouse model of chronologic aging. Methods: After 50 weeks of chronologic aging, 44 female BALB/c nude mice were classified into four groups: (1) negative control, (2) mice injected subcutaneously with fat on the back skin (0.5 cm3), (3) mice injected with adipose-derived stem cells (1 × 105 cells in 0.5 cm3 Hanks balanced salt solution), and (4) mice injected with both fat (0.5 cm3) and adipose-derived stem cells (1 × 105 cells in 0.5 cm3 Hanks balanced salt solution). The degree of wrinkling was evaluated using replica analysis, and skin biopsies were performed after 4 weeks. The dermal thickness and density of collagen were determined. Type I procollagen and matrix metalloproteinase levels were determined using real-time polymerase chain reaction and Western blot analysis. Tropoelastin, fibrillin-1, and CD31 levels were evaluated using immunohistochemistry. Results: Based on the total wrinkle area, there was significant wrinkle reduction in the fat-treated and adipose-derived stem cell with fat–treated groups. Type I procollagen mRNA and collagen levels were significantly higher in the adipose-derived stem cell with fat–treated group than in the adipose-derived stem cell–treated and the fat-treated groups. In addition, the adipose-derived stem cells with fat graft group exhibited significantly higher CD31 expression level than the adipose-derived stem cell–treated and the fat-treated groups. Conclusion: Both adipose-derived stem cells and fat graft have a wrinkle-reducing effect and synergistically affect collagen synthesis and neovascularization.