Mesenchymal stem cells are multipotent cells that can differentiate into cardiomyocytes and vascular endothelial cells. Here we show, using cell sheet technology, that monolayered mesenchymal stem cells have multipotent and self-propagating properties after transplantation into infarcted rat hearts. We cultured adipose tissue-derived mesenchymal stem cells characterized by flow cytometry using temperature-responsive culture dishes. Four weeks after coronary ligation, we transplanted the monolayered mesenchymal stem cells onto the scarred myocardium. After transplantation, the engrafted sheet gradually grew to form a thick stratum that included newly formed vessels, undifferentiated cells and few cardiomyocytes. The mesenchymal stem cell sheet also acted through paracrine pathways to trigger angiogenesis. Unlike a fibroblast cell sheet, the monolayered mesenchymal stem cells reversed wall thinning in the scar area and improved cardiac function in rats with myocardial infarction. Thus, transplantation of monolayered mesenchymal stem cells may be a new therapeutic strategy for cardiac tissue regeneration.

Background-Pluripotent

No abstract

. Prostacyclin agonist with thromboxane synthase inhibitory activity (ONO-1301) attenuates bleomycin-induced pulmonary fibrosis in mice. Am J Physiol Lung Cell Mol Physiol 290: L59 -L65, 2006. First published September 9, 2005 doi:10.1152/ajplung.00042.2005The balance between prostacyclin and thromboxane A2 (TXA2) plays an important role in pulmonary homeostasis. However, little information is available regarding the therapeutic potency of these prostanoids for pulmonary fibrosis. We have recently developed ONO-1301, a novel long-acting prostacyclin agonist with thromboxane synthase inhibitory activity. Thus we investigated whether repeated administration of ONO-1301 attenuates bleomycin-induced pulmonary fibrosis in mice. After intratracheal injection of bleomycin or saline, mice were randomized to receive repeated subcutaneous administration of ONO-1301 or vehicle. Bronchoalveolar lavage (BAL) and histological analyses were performed at 3, 7, and 14 days after bleomycin injection. In vitro studies using mouse lung fibroblasts were also performed. ONO-1301 significantly attenuated the development of bleomycin-induced pulmonary fibrosis, as indicated by significant decreases in Ashcroft score and lung hydroxyproline content. ONO-1301 significantly reduced total cell count, neutrophil count, and total protein level in BAL fluid in association with a marked reduction of TXB 2. A single administration of ONO-1301 significantly increased plasma cAMP level for Ͼ2 h. In vitro, ONO-1301 and a cAMP analog dose-dependently reduced cell proliferation in mouse lung fibroblasts. The reduction in cell proliferation by ONO-1301 was attenuated by a protein kinase A (PKA) inhibitor. Furthermore, bleomycin mice treated with ONO-1301 had a significantly higher survival rate than those given vehicle. These results suggest that repeated administration of ONO-1301 attenuates the development of bleomycin-induced pulmonary fibrosis and improves survival in bleomycin mice, at least in part by inhibition of TXA 2 synthesis and activation of the cAMP/PKA pathway. adenosine 3Ј,5Ј-cyclic monophosphate; fibroblast; neutrophil; survival IDIOPATHIC PULMONARY FIBROSIS (IPF) is a life-threatening disease characterized by progressive dyspnea and worsening of pulmonary function (6,22). The pathological features of IPF are fibroblast proliferation with increased amounts of extracellular matrix and varying degrees of persistent inflammation of the alveolar septa (22). Thus a novel therapeutic strategy against these abnormalities may be effective for the treatment of IPF.Prostanoids, which are metabolites of arachidonic acid, are important regulators of pulmonary homeostasis. Prostacyclin inhibits migration, proliferation, and collagen synthesis in fibroblasts (14, 29). Conversely, thromboxane A 2 (TXA 2 ) promotes fibroblast proliferation, increases pulmonary vascular permeability, and induces lung inflammation (18,21,24). Interestingly, a recent study has demonstrated that the decreased ratio of prostacyclin synthesis to thromboxane synthesis is...

HighlightsEndoscopy is necessary for management of gastric volvulus.Endoscopic reduction is effective as first aid for gastric volvulus.Endoscopic gastropexy is available for gastric volvulus in elderly patients.Laparoscopic gastropexy can be an alternative to hernia repair in poor condition.