Clostridium ventriculi in a cynomolgus monkey with acute gastric dilatation and rupture: A case report.

Acute gastric dilatation (AGD) is one of the most prevalent and life-threatening diseases in nonhuman primates worldwide. However, the etiology of this syndrome has not been determined. Recently, sudden death occurred in a 7-year-old female cynomolgus monkey with a history of fecal microbiota transplantation using diarrheic stools.

Design principles for electrically driven Luttinger liquid-fed plasmonic nanoantennas.

Electrons injected into one-dimensional (1D) metals are efficiently converted into infrared plasmons because the unique property of the Luttinger liquid, a strongly correlated electronic matter in one-dimensional (1D) metals, prohibits excitations of other quasiparticles. Using the Luttinger liquid behavior, the electrically driven 1D metals can be used as a feed for optical nanoantennas. Nanoantennas can couple the 1D Luttinger liquid plasmons in the feed to the radiating photons in free space.

Protective effects of human umbilical cord blood‑derived mesenchymal stem cells against dexamethasone‑induced apoptotic cell death in hair follicles.

Alopecia is a common and distressing condition, and developing new therapeutic agents to prevent hair loss is important. Human umbilical cord blood‑derived mesenchymal stem cells (hUCB‑MSCs) have been studied intensively in regenerative medicine. However, the therapeutic potential of these cells against hair loss and hair organ damage remains unclear, and the effects of hUCB‑MSC transplantation on hair loss require evaluation.

Cobalt Chloride Enhances the Anti-Inflammatory Potency of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells through the ERK-HIF-1-MicroRNA-146a-Mediated Signaling Pathway.

Human mesenchymal stem cells (hMSCs), including human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs), which have high proliferation capacity and immunomodulatory properties, are considered to be a good candidate for cell-based therapies. hMSCs show enhanced therapeutic effects via paracrine secretion or cell-to-cell contact that modulates inflammatory or immune reactions. Here, treatment with cobalt chloride (CoCl) was more effective than naïve hUCB-MSCs in suppressing inflammatory responses in a coculture system with phytohemagglutinin- (PHA-) activated human peripheral blood mononuclear cells (hPBMCs).

Human umbilical cord blood mesenchymal stem cells engineered to overexpress growth factors accelerate outcomes in hair growth.

Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth.

Optimization of culture conditions for rapid clinical-scale expansion of human umbilical cord blood-derived mesenchymal stem cells.

Background: Mesenchymal stem cells (MSCs) have broad-spectrum therapeutic effects in various diseases, and thus have many clinical applications. However, it is difficult to produce sufficient numbers of MSCs for clinical use, and improved culture systems are required. Here, we report the effects of calcium (Ca) and hypoxia on the proliferation of human umbilical cord blood-derived MSCs (hUCB-MSCs).

Cobalt chloride induces neuronal differentiation of human mesenchymal stem cells through upregulation of microRNA-124a.

Human mesenchymal stem cells (hMSCs) are known to have the capacity to differentiate into various cell types, including neurons. To examine our hypothesis that miRNA was involved in neuronal differentiation of hMSCs, CoCl2, a hypoxia-mimicking agent was used to induce neuronal differentiation, which was assessed by determining the expression of neuronal markers such as nestin and Tuj1. Treatment of hMSCs with CoCl2 led to increased expression of miR-124a, a neuron-specific miRNA.

Functional expression of smooth muscle-specific ion channels in TGF-β(1)-treated human adipose-derived mesenchymal stem cells.

Human adipose tissue-derived mesenchymal stem cells (hASCs) have the power to differentiate into various cell types including chondrocytes, osteocytes, adipocytes, neurons, cardiomyocytes, and smooth muscle cells. We characterized the functional expression of ion channels after transforming growth factor-β1 (TGF-β1)-induced differentiation of hASCs, providing insights into the differentiation of vascular smooth muscle cells. The treatment of hASCs with TGF-β1 dramatically increased the contraction of a collagen-gel lattice and the expression levels of specific genes for smooth muscle including α-smooth muscle actin, calponin, smooth mucle-myosin heavy chain, smoothelin-B, myocardin, and h-caldesmon.

Lysophosphatidic acid activates TGFBIp expression in human corneal fibroblasts through a TGF-β1-dependent pathway.

Granular corneal dystrophy type 2 (GCD2) is an autosomal dominant disease caused by a R124H point mutation in the transforming growth factor-β-induced gene (TGFBI). However, the cellular role of TGFBI and the regulatory mechanisms underlying corneal dystrophy pathogenesis are still poorly understood. Lysophosphatidic acid (LPA) refers to a small bioactive phospholipid mediator produced in various cell types, and binds G protein-coupled receptors to enhance numerous biological responses, including cell growth, inflammation, and differentiation.

Tumor necrosis factor-α-activated human adipose tissue-derived mesenchymal stem cells accelerate cutaneous wound healing through paracrine mechanisms.

Human adipose tissue-derived mesenchymal stem cells (ASCs) stimulate regeneration of injured tissues by secretion of various cytokines and chemokines. Wound healing is mediated by multiple steps including inflammation, epithelialization, neoangiogenesis, and proliferation. To explore the paracrine functions of ASCs on regeneration of injured tissues, cells were treated with tumor necrosis factor-α (TNF-α), a key inflammatory cytokine, and the effects of TNF-α-conditioned medium (CM) on tissue regeneration were determined using a rat excisional wound model.

Mesenchymal stem cells stimulate angiogenesis in a murine xenograft model of A549 human adenocarcinoma through an LPA1 receptor-dependent mechanism.

Carcinoma-associated fibroblasts play a key role in tumorigenesis and metastasis by providing a tumor-supportive microenvironment. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to carcinoma-associated fibroblasts expressing α-smooth muscle actin, vascular endothelial growth factor, and stromal cell-derived factor-1. A549 conditioned medium-induced differentiation of hASCs to carcinoma-associated fibroblasts was completely abrogated by treatment of hASCs with Ki16425, a lysophosphatidic acid receptor antagonist, or knockdown of lysophosphatidic acid receptor 1 (LPA(1)) expression in hASCs with small interfering RNA or lentiviral short hairpin RNA.

Lysophosphatidic acid-induced expression of periostin in stromal cells: Prognoistic relevance of periostin expression in epithelial ovarian cancer.

Lysophosphatidic acid (LPA) is a bioactive lipid crucial for the initiation and progression of ovarian cancer. Identification of LPA-induced biomarkers is necessary for predicting prognosis of ovarian cancer patients. Here we report periostin, an extracellular matrix protein, as an LPA-induced protein in stromal cells and as a prognostic marker in patients with epithelial ovarian cancer (EOC).

Ovarian cancer-derived lysophosphatidic acid stimulates secretion of VEGF and stromal cell-derived factor-1 alpha from human mesenchymal stem cells.

Lysophosphatidic acid (LPA) stimulates growth and invasion of ovarian cancer cells and tumor angiogenesis. Cancer-derived LPA induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) to alpha-smooth muscle actin (alpha-SMA)-positive cancer-associated fibroblasts. Presently, we explored whether cancer-derived LPA regulates secretion of pro-angiogenic factors from hASCs.

Thromboxane a(2) induces differentiation of human mesenchymal stem cells to smooth muscle-like cells.

Thromboxane A(2) (TxA(2)) is involved in smooth muscle contraction and atherosclerotic vascular diseases. Accumulating evidence suggests a pivotal role for mesenchymal stem cells (MSCs) in vascular remodeling. In the present study, we demonstrate for the first time that the TxA(2) mimetic U46619 induces differentiation of human adipose tissue-derived MSCs (hADSCs) to smooth muscle-like cells, as demonstrated by increased expression of smooth muscle-specific contractile proteins such as alpha-smooth muscle actin (alpha-SMA), calponin, smoothelin, and smooth muscle-myosin heavy chain.

A Rho kinase/myocardin-related transcription factor-A-dependent mechanism underlies the sphingosylphosphorylcholine-induced differentiation of mesenchymal stem cells into contractile smooth muscle cells.

Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hADSCs) to smooth muscle cells (SMCs). In the present study, we characterized contractile and ion channel properties of SMCs differentiated from hADSCs (hADSC-SMCs) as a result of SPC treatment, and we investigated the molecular mechanisms involved in the SPC-induced differentiation. Using in vitro collagen gel lattice contraction and whole cell patch clamp, we showed that the hADSC-SMCs expressed functional L-type voltage-gated Ca2+ channels and contractile activities in response to KCl, carbachol, and the L-type Ca2+ channel opener Bay K8644, whereas the L-type Ca2+ channel blocker nifedipine abrogated the contractility of hADSC-SMCs.

Bradykinin-induced expression of alpha-smooth muscle actin in human mesenchymal stem cells.

Phenotypic expression of alpha-smooth muscle actin (alpha-SMA), a smooth muscle marker, has been implicated in vascular diseases, fibrosis, wound healing, and tissue remodeling. Bradykinin (BK), a vasoactive peptide produced during tissue injury, plays a key role in inflammatory and vascular responses associated with tissue injury. In the present study, we demonstrated for the first time that BK treatment increased alpha-SMA expression in human adipose tissue-derived mesenchymal stem cells (hADSCs).

Angiotensin II-induced differentiation of adipose tissue-derived mesenchymal stem cells to smooth muscle-like cells.

Angiotensin II (Ang II) is involved in the development of cardiovascular disease and vascular remodeling. In this study, we demonstrate that treatment of human adipose tissue-derived mesenchymal stem cells (hADSCs) with Ang II increased the expression of smooth muscle-specific genes, including alpha-smooth muscle actin (alpha-SMA), calponin, h-caldesmon, and smooth muscle myosin heavy chain (SM-MHC), and also elicited the secretion of transforming growth factor-beta1 (TGF-beta1) and delayed phosphorylation of Smad2. The Ang II-induced expression of alpha-SMA and delayed phosphorylation of Smad2 were blocked by pretreatment of the cells with a TGF-beta type I receptor kinase inhibitor, SB-431542, small interference RNA-mediated depletion of endogenous Smad2, and adenoviral expression of Smad7.

Cancer-derived lysophosphatidic acid stimulates differentiation of human mesenchymal stem cells to myofibroblast-like cells.

Lysophosphatidic acid (LPA) is enriched in ascites of ovarian cancer patients and is involved in growth and invasion of ovarian cancer cells. Accumulating evidence suggests cancer-associated myofibroblasts play a pivotal role in tumorigenesis through secreting stromal cell-derived factor-1 (SDF-1). In the present study, we demonstrate that LPA induces expression of alpha-smooth muscle actin (alpha-SMA), a marker for myofibroblasts, in human adipose tissue-derived mesenchymal stem cells (hADSCs).

Lysophosphatidic acid in malignant ascites stimulates migration of human mesenchymal stem cells.

Lysophosphatidic acid (LPA) is elevated in ascites of ovarian cancer patients and is involved in growth and invasion of ovarian cancer cells. Accumulating evidence suggests a pivotal role of mesenchymal stem cells (MSCs) or stromal cells in tumorigenesis. In the present study, we demonstrated that ascites from ovarian cancer patients and LPA increased migration of human MSCs.

Sphingosylphosphorylcholine stimulates expression of fibronectin through TGF-beta1-Smad-dependent mechanism in human mesenchymal stem cells.

Sphingosylphosphorylcholine (SPC) has been reported to stimulate the expression of fibronectin (FN), which plays a key role in cell recruitment and adhesion during wound healing. In a previous study, we reported that SPC induces differentiation of human adipose tissue-derived mesenchymal stem cells (hATSCs) to smooth muscle-like cell types through ERK-dependent autocrine secretion of TGF-beta1 and delayed activation of the TGF-beta1-Smad pathway. In the present study, we demonstrated that SPC dose- and time-dependently increased the expression of FN in hATSCs.

Oncostatin M promotes osteogenesis and suppresses adipogenic differentiation of human adipose tissue-derived mesenchymal stem cells.

Oncostatin M (OSM) is a multifunctional cytokine of the interleukin-6 family and has been implicated in embryonic development, differentiation, inflammation, and regeneration of liver and bone. In the present study, we demonstrated that treatment of human adipose mesenchymal stem cells (hADSCs) with OSM-attenuated adipogenic differentiation, as indicated by decreased accumulation of intracellular lipid droplets and down-regulated expression of adipocytic markers, such as lipoprotein lipase and PPARgamma. However, OSM treatment stimulated osteogenic differentiation, as demonstrated by the increase in matrix mineralization and expression levels of osteogenic differentiation markers, including alkaline phosphatase, Runx2, and osteocalcin.

Sphingosylphosphorylcholine induces apoptosis of endothelial cells through reactive oxygen species-mediated activation of ERK.

Sphingosylphosphorylcholine (SPC) produces reactive oxygen species (ROS) in MS1 pancreatic islet endothelial cells. In the present study, we explored the physiological significance of the SPC-induced ROS generation in endothelial cells. SPC induced cell death of MS1 cells at higher than 10 microM concentration through a caspase-3-dependent pathway.

Sphingosylphosphorylcholine induces differentiation of human mesenchymal stem cells into smooth-muscle-like cells through a TGF-beta-dependent mechanism.

Mesenchymal stem cells (MSCs) can differentiate into diverse cell types including adipogenic, osteogenic, chondrogenic and myogenic lineages. In the present study, we demonstrated for the first time that sphingosylphosphorylcholine (SPC) induces differentiation of human adipose-tissue-derived mesenchymal stem cells (hATSCs) to smooth-muscle-like cell types. SPC increased the expression levels of several smooth-muscle-specific genes, such as those for alpha-smooth-muscle actin (alpha-SMA), h1-calponin and SM22alpha, as effectively as transforming growth factor beta (TGF-beta1) and TGF-beta3.

Oncostatin M decreases adiponectin expression and induces dedifferentiation of adipocytes by JAK3- and MEK-dependent pathways.

Adiponectin, an adipokine secreted from adipocytes, plays a crucial role in the regulation of glucose and lipid metabolism. In the present study, we examine the role of the IL-6 family of cytokines in the expression of adiponectin in human adipocytes derived from human adipose tissue-derived stromal cells. Oncostatin M (OSM), but not IL-6, attenuated the expression level of adiponectin dose- and time-dependently, and the inhibitory effect of OSM on adiponectin expression was as potent as that of TNF-alpha.

Lysophosphatidylcholine suppresses apoptosis and induces neurite outgrowth in PC12 cells through activation of phospholipase D2.

Lysophosphatidylcholine (LPC) is a bioactive lipid generated by phospholipase A2-mediated hydrolysis of phosphatidylcholine. In the present study, we demonstrate that LPC stimulates phospholipase D2 (PLD2) activity in rat pheochromocytoma PC12 cells. Serum deprivation induced cell death of PC12 cells, as demonstrated by decreased viability, DNA fragmentation, and increased sub-G1 fraction of cell cycle.