Human stem cells and articular cartilage regeneration.

The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation

前腹側脳室周囲核における性差発現タンパク質の探索と機能解析

筑波大学 (University of Tsukuba)201

Ghrelin and Functional Dyspepsia

The majority of patients with dyspepsia have no identifiable cause of their disease, leading to a diagnosis of functional dyspepsia (FD). While a number of different factors affect gut activity, components of the nervous and endocrine systems are essential for normal gut function. Communication between the brain and gut occurs via direct neural connections or endocrine signaling events. Ghrelin, a peptide produced by the stomach, affects gastric motility/emptying and secretion, suggesting it may play a pathophysiological role in FD. It is also possible that the functional abnormalities in FD may affect ghrelin production in the stomach. Plasma ghrelin levels are reported to be altered in FD, correlating with FD symptom score. Furthermore, some patients with FD suffer from anorexia with body-weight loss. As ghrelin increases gastric emptying and promotes feeding, ghrelin therapy may be a new approach to the treatment of FD

Treatment of ununited femoral neck fractures in young adults using low-intensity pulsed ultrasound: Report of 2 cases

AbstractIntroductionDelayed union and non-union of displaced femoral neck fractures remains a difficult clinical problem for orthopaedic surgeons. In the physiologically young patient, every effort should be made to preserve the native hip joint. We present two cases of ununited femoral neck fractures in young adults who were successfully treated with low-intensity pulsed ultrasound (LIPUS) and showed satisfactory results.Presentation of case 1A 41-year-old woman was involved in a motor vehicle crash and was diagnosed with displaced femoral neck fracture. Eleven months after internal fixation, a computed tomography (CT) scan revealed the presence of non-union of the femoral neck. LIPUS treatment was therefore initiated. After eight months, the fracture was completely consolidated.Presentation of case 2A 39-year-old man was involved in a cycling accident and was diagnosed with displaced femoral neck fracture. Thirteen weeks after internal fixation, a CT scan revealed delayed union of the femoral neck. LIPUS treatment was therefore initiated. After six months, the fracture was completely consolidated.ConclusionWe suggest use of LIPUS as a possible treatment approach for delayed union and non-union of displaced femoral neck fractures in young patients before considering further surgical intervention

IL-6–dependent spontaneous proliferation is required for the induction of colitogenic IL-17–producing CD8+ T cells

We propose a novel role for interleukin (IL) 6 in inducing rapid spontaneous proliferation (SP) of naive CD8+ T cells, which is a crucial step in the differentiation of colitogenic CD8+ T cells. Homeostasis of T cells is regulated by two distinct modes of cell proliferation: major histocompatibility complex/antigen–driven rapid SP and IL-7/IL-15–dependent slow homeostatic proliferation. Using our novel model of CD8+ T cell–dependent colitis, we found that SP of naive CD8+ T cells is essential for inducing pathogenic cytokine-producing effector T cells. The rapid SP was predominantly induced in mesenteric lymph nodes (LNs) but not in peripheral LNs under the influence of intestinal flora and IL-6. Indeed, this SP was markedly inhibited by treatment with anti–IL-6 receptor monoclonal antibody (IL-6R mAb) or antibiotic-induced flora depletion, but not by anti–IL-7R mAb and/or in IL-15–deficient conditions. Concomitantly with the inhibition of SP, anti–IL-6R mAb significantly inhibited the induction of CD8+ T cell–dependent autoimmune colitis. Notably, the transfer of naive CD8+ T cells derived from IL-17−/− mice did not induce autoimmune colitis. Thus, we conclude that IL-6 signaling is crucial for SP under lymphopenic conditions, which subsequently caused severe IL-17–producing CD8+ T cell–mediated autoimmune colitis. We suggest that anti–IL-6R mAb may become a promising strategy for the therapy of colitis

NK cells control tumor-promoting function of neutrophils in mice

Although NK cells are recognized as direct antitumor effectors, the ability of NK cells to control cancer-associated inflammation, which facilitates tumor progression, remains unknown. In this study, we demonstrate that NK cells control tumor-promoting inflammation through functional modification of neutrophils. NK cells control the tumor-promoting function of neutrophils through an IFNgamma-dependent mechanism. Tumor progression in an NK cell-depleted host is diminished when the IL17A-neutrophil axis is absent. In NK cell-depleted mice, neutrophils acquire a tumor-promoting phenotype, characterized by up-regulation of VEGF-A expression, which promotes tumor growth and angiogenesis. A VEGFR inhibitor which preferentially suppressed tumor growth in NK cell-depleted mice was dependent on neutrophils. Furthermore, the systemic neutropenia caused by an anti-metabolite treatment showed an anti-cancer effect only in mice lacking NK cells. Thus, NK cells likely control the tumor-promoting and angiogenic function of neutrophils