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Human synovial mesenchymal stem cells (hSMSCs) are a promising cell source for cartilage regeneration because of their superior chondrogenic potential in vitro. This study aimed to further optimize the conditions for inducing chondrogenesis of hSMSCs, focusing on the dose of dexamethasone in combination with transforming growth factor-β3 (TGFβ3) and/or bone morphogenetic protein-2 (BMP2). When hSMSCs-derived aggregates were cultured with TGFβ3, dexamethasone up to 10 nM promoted chondrogenesis, but attenuated it with heterogeneous tissue formation when used at concentrations over than 100 nM. On the other hands, BMP2-induced chondrogenesis was remarkably disturbed in the presence of more than 10 nM dexamethasone along with unexpected adipogenic differentiation. In the presence of both TGFβ3 and BMP2, dexamethasone dose dependently promoted cartilaginous tissue formation as judged by tissue volume, proteoglycan content, and type 2 collagen expression, whereas few adipocytes were detected in the formed tissue when cultures were supplemented with over 100 nM dexamethasone. Even in chondrogenic conditions, dexamethasone thus affected hSMSCs differentiation not only toward chondrocytes, but also towards adipocytes dependent on the dose and combined growth factor. These findings have important implications regarding the use of glucocorticoids in in vitro tissue engineering for cartilage regeneration using hSMSCs.

Various approaches to treat articular cartilage have been widely investigated due to its poor intrinsic healing capacity. Stem cell-based therapy could be a promising approach as an alternative to chondrocyte-based therapy and some of these therapies have been already applied in clinical condition. This review discusses the current development of stem cell-based therapies in cartilage repair, specifically focusing on scaffold-free approaches.

Background Head elevation can restore airway patency during anesthesia, although its effect may be offset by concomitant bite opening or accidental neck flexion. The aim of this study is to examine the effect of head elevation on the passive upper airway collapsibility during propofol anesthesia. Method Twenty male subjects were studied, randomized to one of two experimental groups: Fixed-jaw or Free-jaw. Propofol infusion was used for induction and to maintain blood concentration constant at a target level between 1.5 and 2.0 μg/ml. Nasal mask pressure (PN) was intermittently reduced to evaluate the upper airway collapsibility (passive PCRIT) and upstream resistance (RUS) at each level of head elevation (0, 3, 6, & 9 cm). We measured the Frankfort plane (head flexion) and the mandible plane (jaw opening) angles at each level of head elevation. Analysis of variance was used to determine effect of head elevation on PCRIT, head flexion and jaw opening within each group. Results In both groups the Frankfort plane and mandible plane angles increased as with head elevation (P < 0.05), although the mandible plane angle was lower in the Free-jaw group (i.e., increased jaw opening). In the Fixed-jaw group, head elevation decreased upper airway collapsibility (PCRIT ~ −7 cmH2O at greater than 6 cm elevation) compared to the baseline position (PCRIT ~ −3 cmH2O at 0 cm elevation; P < 0.05). Conclusion We demonstrate that elevating the head position by 6 cm while ensuring mouth closure (centric occlusion) produces substantial decreases in upper airway collapsibility and maintains upper airway patency during anesthesia.

As an alternative to chondrocytes-based cartilage repair, stem cell-based therapies have been investigated. Specifically, human synovium-derived stem cells (hSSCs) are a promising cell source based on their highly capacities for chondrogenesis, but some methodological improvements are still required towards optimal cartilage regenera-

To investigate the role of interleukin (IL)-33 in rheumatoid arthritis (RA) patients, we measured the serum levels of IL-33 in RA patients before and after the administration of etanercept. Twenty-four patients with RA were treated with etanercept. Clinical and laboratory examinations, including serum levels of C-reactive protein (CRP) and hemoglobin (Hb); white blood cell (WBC) and red blood cell (RBC) counts; and the Disease Activity Score of 28 joints including CRP (DAS28-CRP), were performed at the baseline and at 3 and 6 months after the initial treatment with etanercept. The mean serum IL-33 levels had decreased significantly at 3 and 6 months after the initial treatment with etanercept. Serum IL-33 levels showed a significant correlation with the number of tender joints, CRP, DAS28-CRP, and the WBC count, and an inverse correlation with the RBC count and Hb level. These findings indicated that the decrease of serum IL-33 levels was a novel function of etanercept, shown for the first time in this study. Measurement of serum levels of IL-33 may become a useful control marker for RA treatment.

Objectives: To investigate chymase involvement in idiopathic macular hole onset, the effects of chymase on monkey eyes and cultured Müller cells were investigated. Methods: Immunohistochemistry using antinestin and antiglial fibrillary acidic protein antibodies was performed in a normal monkey eye. After chymase was injected into the monkey vitreous, histological changes in the retina were evaluated using the TdT-mediated dUTP nick-end labeling (TUNEL) assay. Expression of c-kit, a stem cell factor receptor, and nestin was examined in porcine Müller cells cultured with basic fibroblast growth factor. The effects of chymase on proliferation and TUNEL staining in Müller cells were also examined. Results: The number of nestin and glial fibrillary acidic protein-positive cells was higher in the macula than in other regions. Thickening of the posterior hyaloid membrane and some apoptotic cells were found in the macula of chymase-treated eyes. The expression of c-kit and nestin in Müller cells was shown and enhanced when cultured with basic fibroblast growth factor. Exposure to chymase inhibited Müller cell proliferation and produced TUNEL-positive cells. Conclusions: There might be Müller cells possessing atypical properties near the macular region and chymase might cause fibrosis and apoptosis through these cells. These findings suggest that increased chymase activity may result in idiopathic macular hole onset.

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