Regenerative Therapies Using Cell Sheet-Based Tissue Engineering for Cardiac Disease

At present, cardiac diseases are a major cause of morbidity and mortality in the world. Recently, a cell-based regenerative medicine has appeared as one of the most potential and promising therapies for improving cardiac diseases. As a new generational cell-based regenerative therapy, tissue engineering is focused. Our laboratory has originally developed cell sheet-based scaffold-free tissue engineering. Three-dimensional myocardial tissue fabricated by stacking cardiomyocyte sheets, which are tightly interconnected to each other through gap junctions, beats simultaneously and macroscopically and shows the characteristic structures of native heart tissue. Cell sheet-based therapy cures the damaged heart function of animal models and is clinically applied. Cell sheet-based tissue engineering has a promising and enormous potential in myocardial tissue regenerative medicine and will cure many patients suffering from severe cardiac disease. This paper summarizes cell sheet-based tissue engineering and its satisfactory therapeutic effects on cardiac disease

ヒト肝細胞癌においてherpesvirus entry mediatorの発現がもたらす影響

BACKGROUND: Herpes virus entry mediator (HVEM), also known as tumour necrosis factor receptor (TNFR) superfamily 14, regulates a variety of physiological and pathological responses in both innate and acquired immunity. Although HVEM is also suggested to be a critical regulator in tumours, actual roles in human cancer are largely unknown. This study aimed to clarify clinical importance of HVEM in human hepatocellular carcinoma (HCC). PATIENTS AND METHODS: We studied HVEM expression in 150 HCC patients to explore its clinical relevance, and we examined tumour infiltrating T cells and local immune status of them. RESULTS: HVEM was expressed in HCC cells, while no or only limited expression was observed in normal tissues in the liver. Tumour HVEM expression was significantly correlated with age, serum protein induced by vitamin K absence or antagonist-II (PIVKA-II) level, vascular invasion and tumour node metastasis (TNM) stage. Furthermore, tumour HVEM expression significantly correlated with postoperative recurrence and survival. Importantly, multivariate analysis indicated that the HVEM status had an independent prognostic value. Furthermore, HVEM status was inversely correlated with tumour-infiltrating CD4(+), CD8(+) and CD45RO(+) lymphocytes. In addition, it was also associated with reduced expression of perforin, granzyme B and interferon-γ (IFN-γ). Taken together, tumour-expressing HVEM plays a functionally important role in HCC. CONCLUSION: Tumour-expressing HVEM plays a critical role in human HCC, possibly through regulating immune evasion. Therefore, targeting HVEM may be a novel promising therapeutic strategy for HCC.博士（医学）・乙第1359号・平成27年5月28日Copyright © 2014 Elsevier Ltd

Rat limbal epithelial side population cells exhibit a distinct expression of stem cell markers that are lacking in side population cells from the central cornea

AbstractThe side population (SP) phenotype is shared by stem cells in various tissues and species. Here we demonstrate SP cells with Hoechst dye efflux were surprisingly collected from the epithelia of both the rat limbus and central cornea, unlike in human and rabbit eyes. Our results show that rat limbal SP cells have a significantly higher expression of the stem cell markers ABCG2, nestin, and notch 1, compared to central corneal SP cells. Immunohistochemistry also revealed that ABCG2 and the epithelial stem/progenitor cell marker p63 were expressed only in basal limbal epithelial cells. These results demonstrate that ABCG2 expression is closely linked to the stem cell phenotype of SP cells