On the basis of the current evidence, EAT seems to be an effective marker in the prediction of CAD.

MSC transplantation can inhibit function of CFs by secreting antifibrotic factors such as ADM, resulting in decrease of myocardial fibrosis.

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Summary We aimed to examine the ability of transplanted mesenchymal stem cells (MSCs) to attenuate cardiac fibrosis caused by global heart failure, and investigate the mechanisms that are possibly mediating this effect. Global heart failure was induced in Wistar rats by isoproterenol injection. Four weeks later, MSCs were transplanted by intramyocardial injection, while control groups were treated by injection of cell culture medium alone. Four weeks after transplantation, heart function was assessed, and histologic and molecular analyses conducted. Compared with the medium‐treated group, MSC transplantation significantly decreased the expression of collagens I and III, and matrix metalloproteinase 2 and 9, but heart function was improved in MSC‐treated animals. In addition, expression of antifibrotic factor, hepatocyte growth factor (HGF), was detected in cultured MSCs, suggesting a possible mechanism underlying antifibrotic effects. Importantly, HGF expression levels were higher in MSC‐treated hearts, compared with medium‐treated hearts. Therefore, we could conclude that MSC transplantation can attenuate myocardial fibrosis in a rat model of global heart failure, and this may be at least partially mediated by paracrine signaling from MSCs via antifibrotic factors such as HGF.

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Stem cells transplantation holds great promise for the treatment of ischemic diseases through functional revascularization. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) are also an ideal candidate for cell-based bioengineering. Herein, we report on the development of a simple and effective protocol to isolate UC-MSCs, and confirm their endothelial potential both in vitro and in vivo. UC-MSCs were isolated by a novel explantation technique and induced to differentiate into endothelial-like cells. Then UC-MSCs were transplanted into ischemic mouse model and cultured on 3D gel/MMT-CS composite scaffolds. Morphological and proliferation assessments show that sufficient UC-MSCs can be generated during a relatively short culture period with explantation technique. Increased expression of endothelial-specific markers (KDR and vWF), and functional markers (ac-LDL uptake and UEA-1 binding), indicate that functional endothelial progenitor cells are induced after 9 days of in vitro culture. In an ischemic hindlimb mouse model, the ratio of ischemic/nonischemic limb perfusion 4 weeks after MSCs transplantation reached 0.84 +/- 0.09. The capillary density of this group was 2.57-fold greater than that of sham-injected mice (P < 0.05). Immunofluorescence and immunohistological analyses indicate that MSCs may act to salvage the ischemic tissue by incorporating into the local vasculature. In vitro, UC-MSCs were observed to incorporate into 3D gel/MMT-CS composite scaffolds, to secrete extracellular matrix, to remain viable, and to retain their proliferation capacity. In conclusion, UC-MSCs isolated by novel yet simple explantation technique are well suited for application in the development of novel stem cell-based revascularization therapies.

The central role of reactive oxygen species (ROS) in osteoclast differentiation and in bone homeostasis prompted us to characterize the redox regulatory system of osteoclasts. In this report, we describe the expression and functional characterization of PAMM, a CXXC motif-containing peroxiredoxin 2-like protein expressed in bone marrow monocytes on stimulation with M-CSF and RANKL. Expression of wild-type (but not C to G mutants of the CXXC domain) PAMM in HEK293 cells results in an increased GSH=GSSG ratio, indicating a shift toward a more reduced environment. Expression of PAMM in RAW264.7 monocytes protected cells from hydrogen peroxide-induced oxidative stress, indicating that PAMM regulates cellular redox status. RANKL stimulation of RAW 264.7 cells caused a decrease in the GSH=GSSG ratio (reflecting a complementary increase in ROS). In addition, RANKL-induced osteoclast formation requires phosphorylation and translocation of NF-kB and c-Jun. In stably transfected RAW 264.7 cells, PAMM overexpression prevented the reduction of GSH=GSSG induced by RANKL. Concurrently, PAMM expression completely abolished RANKL-induced p100 NF-kB and c-Jun activation, as well as osteoclast formation. We conclude that PAMM is a redox regulatory protein that modulates osteoclast differentiation in vitro. PAMM expression may affect bone resorption in vivo and help to maintain bone mass. Antioxid. Redox Signal. 13, 27-37.

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