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Increasing evidence indicates that the secretome of mesenchymal stem cells (MSCs) has therapeutic potential for the treatment of various diseases, including cartilage disorders. However, the paracrine mechanisms underlying cartilage repair by MSCs are poorly understood. Here, we show that human umbilical cord blood-derived MSCs (hUCB-MSCs) promoted differentiation of chondroprogenitor cells by paracrine action. This paracrine effect of hUCB-MSCs on chondroprogenitor cells was increased by treatment with synovial fluid (SF) obtained from osteoarthritis (OA) patients but was decreased by SF of fracture patients, compared to that of an untreated group. To identify paracrine factors underlying the chondrogenic effect of hUCB-MSCs, the secretomes of hUCB-MSCs stimulated by OA SF or fracture SF were analyzed using a biotin label-based antibody array. Among the proteins increased in response to these two kinds of SF, thrombospondin-2 (TSP-2) was specifically increased in only OA SF-treated hUCB-MSCs. In order to determine the role of TSP-2, exogenous TSP-2 was added to a micromass culture of chondroprogenitor cells. We found that TSP-2 had chondrogenic effects on chondroprogenitor cells via PKCa, ERK, p38/MAPK, and Notch signaling pathways. Knockdown of TSP-2 expression on hUCB-MSCs using small interfering RNA abolished the chondrogenic effects of hUCB-MSCs on chondroprogenitor cells. In parallel with in vitro analysis, the cartilage regenerating effect of hUCB-MSCs and TSP-2 was also demonstrated using a rabbit full-thickness osteochondral-defect model. Our findings suggested that hUCB-MSCs can stimulate the differentiation of locally presented endogenous chondroprogenitor cells by TSP-2, which finally leads to cartilage regeneration.

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These results demonstrate that SVH and SVV correlated with clinical dizziness symptoms in patients with acute unilateral vestibular neuritis. Therefore, SVH and SVV would be useful tools for the evaluation of clinical manifestations of unilateral vestibular neuritis.

Previous studies have shown that mesenchymal stem cell (MSC)-based therapies have varying efficacies for the treatment of various diseases, including cartilage defects. In this study, we demonstrated that the chondrogenic differentiation potential of human umbilical cord bloodderived MSCs (hUCB-MSCs) obtained from different individual donors varies, and we investigated the molecular basis for this variation. Microarray gene expression analysis identified thrombospondin-2 (TSP2) as a candidate gene underlying the interindividual variation in the chondrogenic differentiation potential of hUCB-MSCs. To assess the association between TSP-2 and the differentiation potential, we evaluated chondrogenic differentiation of hUCB-MSCs treated with TSP2 siRNA. In addition, we studied the effect of supplementing exogenous recombinant TSP-2 on TSP2 siRNA-treated hUCB-MSCs. We found that TSP-2 autocrinally promoted chondrogenic differentiation of hUCB-MSCs via the Notch signaling pathway, which was confirmed in MSCs from other sources such as bone marrow and adipose tissue. Interestingly, we observed that TSP-2 attenuated hypertrophy, which inevitably occurs during chondrogenic differentiation of hUCB-MSCs. Our findings indicated that the variable chondrogenic differentiation potential of MSCs obtained from different donors is influenced by the TSP-2 level in the differentiating cells. Thus, the TSP-2 level can be used as a marker to select MSCs with superior chondrogenic differentiation potential for use in cartilage regeneration therapy. STEM CELLS 2015;33:3291-3303 SIGNIFICANCE STATEMENTThis study demonstrated MSCs obtained from different donors vary in their chondrogenic differentiation potential, which is influenced by TSP-2 levels. It also provided further data showing that autocrine action of TSP-2 promotes chondrogenic differentiation of MSCs via Notch signaling pathway and suppresses hypertrophy of hUCB-MSC by inhibiting the osteogenic pathway that involves the WNT/b˙-catenin and TGF-b/BMP signal cascades. Based on this dual role of TSP-2, this study suggested that TSP-2 is a new marker for prediction and selection of MSCs with superior chondrogenic differentiation potential for cartilage regeneration therapy.

The use of ultrasound as an enhancement mechanism in the surfactant-aided soil-washing process was examined by conducting desoption tests of soils contaminated with naphthalene or diesel-oil. The experiments were conducted to elucidate the effect of ultrasound on the mass transfer from soil to the aqueous phase using naphthalene-contaminated soil. In addition, the use of ultrasound for the diesel-oil-contaminated soil was investigated under a range of conditions of surfactant concentration, sonication power, duration, soil/liquid ratio, particle size and initial diesel-oil concentration. The ultrasound used in the soil-washing process significantly enhanced the mass transfer rate from the solid phase to the aqueous phase. The removal efficiency of diesel-oil from the soil phase generally increased with longer sonication time, higher power intensity, and large particle size.

Neonatal maple syrup urine disease (MSUD) is associated with diffuse oedema and characteristic MSUD oedema. We present a newborn infant with two coexisting different types of oedema. The myelinated white matter showed a marked decrease in the water apparent diffusion coefficient (ADC) compatible with cytotoxic oedema. The unmyelinated white matter showed an increase in ADC, consistent with vasogenic-interstitial oedema. On follow-up studies, the cytotoxic oedema showed improvement, but the vasogenic-interstitial oedema progressed into brain atrophy.

BackgroundAn increased risk of acute ischemic stroke is recognized among patients with cancer. However, the mechanism behind cancer‐related stroke is unclear. In this study, we determined the presence of associated venous thromboembolism and arterial thromboembolism and their clinical impact on patients with cancer‐related stroke.Methods and ResultsPatients with embolic stroke of undetermined source with or without cancer were evaluated for venous thromboembolism (deep vein thrombosis [DVT] and/or pulmonary embolism) and arterial thromboembolism by using Doppler sonography to determine the presence of lower‐extremity DVT and the microembolic signal of the symptomatic cerebral circulation, respectively. Infarct volume was determined by diffusion‐weighted magnetic resonance imaging. The multivariable linear regression and Cox proportional hazard analysis were used to investigate the effect of DVT and microembolic signal on infarct volume and 1‐year survival, respectively. Of 142 screened patients, 118 were included (37 with, 81 without cancer). Those with cancer had a higher prevalence of DVT or microembolic signal than did the noncancer group (62.2% versus 19.8%; P<0.001). Among patients with cancer‐related stroke, DVT was associated with a greater infarct volume in magnetic resonance imaging (beta, 13.14; 95% CI, 1.62–24.66; P=0.028). Presence of DVT (hazard ratio, 16.79; 95% CI, 2.05–137.75; P=0.009) and microembolic signal (hazard ratio, 8.16; 95% CI, 1.36–48.85; P=0.022) were independent predictors of poor 1‐year survival.ConclusionsPatients with cancer‐associated embolic stroke of undetermined source have an elevated risk of associated venous thromboembolism and arterial thromboembolism, both of which have a significant negative impact on 1‐year survival. The results of this study may enhance our understanding of cancer‐associated stroke and improve risk stratification of patients with this disease.Clinical Trial Registration URL: https://www.clinicaltrials.gov/.Unique identifier: NCT02212496