Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury.

Human ESC-derived mesenchymal stem cell (MSC)-conditioned medium (CM) was previously shown to mediate cardioprotection during myocardial ischemia/reperfusion injury through large complexes of 50-100 nm. Here we show that these MSCs secreted 50- to 100-nm particles. These particles could be visualized by electron microscopy and were shown to be phospholipid vesicles consisting of cholesterol, sphingomyelin, and phosphatidylcholine.

Derivation and characterization of human fetal MSCs: an alternative cell source for large-scale production of cardioprotective microparticles.

The therapeutic effects of mesenchymal stem cells (MSCs) transplantation are increasingly thought to be mediated by MSC secretion. We have previously demonstrated that human ESC-derived MSCs (hESC-MSCs) produce cardioprotective microparticles in pig model of myocardial ischemia/reperfusion (MI/R) injury. As the safety and availability of clinical grade human ESCs remain a concern, MSCs from fetal tissue sources were evaluated as alternatives.

Reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium.

Although paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2'-deoxyguanosine.

Elucidating the secretion proteome of human embryonic stem cell-derived mesenchymal stem cells.

Transplantation of mesenchymal stem cells (MSCs) has been used to treat a wide range of diseases, and the mechanism of action is postulated to be mediated by either differentiation into functional reparative cells that replace injured tissues or secretion of paracrine factors that promote tissue repair. To complement earlier studies that identified some of the paracrine factors, we profiled the paracrine proteome to better assess the relevance of MSC paracrine factors to the wide spectrum of MSC-mediated therapeutic effects. To evaluate the therapeutic potential of the MSC paracrine proteome, a chemically defined serum-free culture medium was conditioned by MSCs derived from human embryonic stem cells using a clinically compliant protocol.

Establishing clonal cell lines with endothelial-like potential from CD9(hi), SSEA-1(-) cells in embryonic stem cell-derived embryoid bodies.

Background: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation.

Methodology/principal Findings: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods.

Derivation of clinically compliant MSCs from CD105+, CD24- differentiated human ESCs.

Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum.

Homocysteine is positively associated with cytokine IL-18 plasma levels in coronary artery bypass surgery patients.

Homocysteine, cytokines (IL-18, IL-6, IL-8) are involved in vascular inflammation and coronary artery disease. Homocysteine influences endothelial IL-6 and IL-8 cytokine expression and release, however, an association between homocysteine and IL-18 has not been previously investigated in endothelial/smooth muscle cells and or in coronary artery disease. We report in 9 coronary artery bypass surgery (CABG) patients a positive correlation r = 0.

Generation of hybrid cell lines with endothelial potential from spontaneous fusion of adult bone marrow cells with embryonic fibroblast feeder.

We have previously isolated mouse embryonic cell lines with endothelial potential using a simple empirical approach. In an attempt to isolate similar cell lines from adult mouse bone marrow (BM), BM cells were cultured on mitotically inactive mouse embryonic fibroblast (MEF) feeder cells. Several cell lines with putative endothelial potential were generated.

Myocardial infarction in the C57BL/6J mouse: a quantifiable and highly reproducible experimental model.

Introduction: The laboratory mouse is a powerful tool in cardiovascular research. In this report, we describe a method for a reproducible mouse myocardial infarction model that would allow subsequent comparative and quantitative studies on molecular and pathophysiological variables.

Methods: (A) The distribution of the major coronary arteries including the septal artery in the left ventricle of the C57BL/6J mice (n=20) was mapped by perfusion of latex dye or fluorescent beads through the aorta.

Embryonic cell lines with endothelial potential: an in vitro system for studying endothelial differentiation.

Objective: Endothelial differentiation is a fundamental process in angiogenesis and vasculogenesis with implications in development, normal physiology, and pathology. To better understand this process, an in vitro cellular system that recapitulates endothelial differentiation and is amenable to experimental manipulations is required.

Methods And Results: Embryonic cell lines that differentiate exclusively into endothelial cells were derived from early mouse embryos using empirical but reproducible culture techniques without viral or chemical transformation.

Hepatic expression of PPARalpha, a molecular target of fibrates, is regulated during inflammation in a gender-specific manner.

Dyslipidemia, inflammation and gender are major risk factors in cardiovascular disease. Here we show that hepatic expression of Peroxisome proliferator-activated receptor alpha (PPARalpha), a nuclear receptor that regulates lipid metabolism and inflammation, is regulated in a gender-specific manner during lipopolysaccharide (LPS)-induced systemic inflammation. Immediately following LPS-induced systemic inflammation, hepatic PPARalpha mRNA level decreased dramatically in mice.

Whole bone marrow transplantation induces angiogenesis following acute ischemia.

Several recent studies have shown that purified subsets of bone marrow (BM) cells can differentiate into endothelial, cardiac, and other cell types. During coronary artery bypass graft (CABG) surgery, sternal BM is routinely discarded. To determine if this BM can be used to induce angiogenesis and augment perfusion of the cardiac tissues after CABG, a simplified and more practical approach of using whole BM extract was tried to determine whether it would be adequate for the induction of BM-derived angiogenesis in experimental acute limb ischemia.