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Various Growth Factors (various + growth_factor)
Selected AbstractsHuman bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor productionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2002Xiaoguang Chen Abstract Treatment of traumatic brain injury (TBI) with bone marrow stromal cells (MSCs) improves functional outcome in the rat. However, the specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Currently, the ability of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue appears limited at best. Tissue replacement, however, is not the only possible compensatory avenue in cell transplantation therapy. Various growth factors have been shown to mediate the repair and replacement of damaged tissue, so trophic support provided by transplanted MSCs may play a role in the treatment of damaged tissue. We therefore investigated the temporal profile of various growth factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of rat brain in vitro and quantitative sandwich enzyme-linked immunosorbent assays (ELISAs) were performed. TBI-conditioned hMSCs cultures demonstrated a time-dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive production of these growth factors by the hMSCs. The ELISA data suggest that transplanted hMSCs may provide therapeutic benefit via a responsive secretion of an array of growth factors that can foster neuroprotection and angiogenesis. © 2002 Wiley-Liss, Inc. [source] Proteomic analysis of membrane proteins expressed specifically in pluripotent murine embryonic stem cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 1 2009Atsushi Intoh Abstract Embryonic stem cells (ESCs) are established from the inner cell mass of preimplantation embryos, are capable of self-renewal, and exhibit pluripotency. Given these unique properties, ESCs are expected to have therapeutic potential in regenerative medicine and as a powerful tool for in vitro differentiation studies of stem cells. Various growth factors and extracellular matrix components regulate the pluripotency and differentiation of ESC progenies. Thus, the cell surface receptors that bind these regulatory factors are crucial for the precise regulation of stem cells. To identify membrane proteins that are involved in the regulation of pluripotent stem cells, the membrane proteins of murine ESCs cultured with or without leukemia inhibitory factor (LIF) were purified and analyzed by quantitative proteomics. 2-D PAGE-based analysis using fluorescently labeled proteins and shotgun-based analysis with isotope-labeled peptides identified 338 proteins, including transmembrane, membrane-binding, and extracellular proteins, which were expressed specifically in pluripotent or differentiated murine ESCs. Functions of the identified proteins revealed cell adhesion molecules, channels, and receptors, which are expected to play important roles in the maintenance of murine ESC pluripotency. Membrane proteins that are expressed in pluripotent ESCs but not in differentiated cells such as Slc16a1 and Bsg could be useful for the selection of the stem cells in vitro. [source] Quantitative analysis of the synthesis and secretion of type VII collagen in cultured human dermal fibroblasts with a sensitive sandwich enzyme-linked immunoassayEXPERIMENTAL DERMATOLOGY, Issue 2 2007Satoshi Amano Abstract:, Type VII collagen is the major component of anchoring fibrils in the epidermal basement membrane. Its expression has been analyzed by immunostaining or Northern blotting, but rarely at the protein level. In this study, we have quantitatively examined the effects of ascorbic acid and various cytokines/growth factors on the protein synthesis and secretion of type VII collagen by human dermal fibroblasts in culture, using a developed, highly sensitive sandwich enzyme-linked immunoassay with two kinds of specific monoclonal antibodies against the non-collagenous domain-1. Ascorbic acid and its derivative induced a twofold increase in type VII collagen synthesis, and markedly increased the secretion of type VII collagen into the medium when compared with the control culture. This effect was not influenced by the presence of transforming growth factor- ,1 (TGF- ,1). The synthesis of type VII collagen was elevated by TGF- ,1, platelet-derived growth factor, tumor necrosis factor- ,, and interleukin-1,, but not by TGF- ,. Thus, our data indicate that the synthesis and secretion of type VII collagen in human dermal fibroblasts are regulated by ascorbate and the enhancement of type VII collagen gene expression by cytokines/growth factors is accompanied with elevated production of type VII collagen at the protein level. [source] Intracutaneous injection of the macrophage-activating lipopeptide-2 (MALP-2) which accelerates wound healing in mice , a phase I trial in 12 patientsEXPERIMENTAL DERMATOLOGY, Issue 12 2008Margarete Niebuhr Abstract:, Chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, are a challenge to physicians and medical personnel and a cause of tremendous discomfort and ensuing loss of quality of life to the patients. Wound healing involves production and action of various growth factors. A novel approach, distinct from the application of single growth factors, is the administration of the macrophage stimulator macrophage-activating lipopeptide-2 (MALP-2). The rationale is based on the finding that macrophages are the main source of several growth factors required for wound healing, which are sequentially released during this process. MALP-2 has previously been shown to be effective in an established animal model with diabetic mice. The purpose of the present phase I study was to establish tolerability of MALP-2 when applied into small cutaneous wounds in human beings. Twelve patients (six females and six males; mean age 66.8 years; range 52,87 years) with different diagnoses were enrolled into the study. An artificial wound was created with a 2-mm diameter skin biopsy punch and a volume of 30 ,l MALP-2 (0.125,1 ,g) or vehicle control, respectively, was injected intracutaneously into the wound and closed with a water-resistant transparent adhesive. Photos were taken daily from every patient up to 6 days, and skin biopsies were performed after 1 week from six patients. We could show in the present study for the first time that MALP-2 caused a transient erythema and was tolerated without any systemic side effects up to a dose of 1 ,g per wound in human beings. In healthy as well as in diabetic patients, MALP-2 induced local inflammation that faded after 48 h. The effectiveness of MALP-2 in the healing of chronic wounds in humans, e.g. in chronic skin ulcers, such as leg ulcers, pressure sores and diabetic foot ulcers, could now be addressed in further studies. [source] Rho exchange factor ECT2 is induced by growth factors and regulates cytokinesis through the N-terminal cell cycle regulator-related domains,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2003Shin'ichi Saito Abstract The ECT2 protooncogene plays a critical role in cytokinesis, and its C-terminal half encodes a Dbl homology-pleckstrin homology module, which catalyzes guanine nucleotide exchange on the Rho family of small GTPases. The N-terminal half of ECT2 (ECT2-N) contains domains related to the cell cycle regulator/checkpoint control proteins including human XRCC1, budding yeast CLB6, and fission yeast Cut5. The Cut5-related domain consists of two BRCT repeats, which are widespread to repair/checkpoint control proteins. ECT2 is ubiquitously expressed in various tissues and cell lines, but elevated levels of ECT2 expression were found in various tumor cell lines and rapidly developing tissues in mouse embryos. Consistent with these findings, induction of ECT2 expression was observed upon stimulation by serum or various growth factors. In contrast to other oncogenes whose expression is induced early in G1, ECT2 expression was induced later, coinciding with the initiation of DNA synthesis. To test the role of the cell cycle regulator/checkpoint control protein-related domains of ECT2 in cytokinesis, we expressed various ECT2 derivatives in U2OS cells, and analyzed their DNA content by flow cytometry. Expression of the N-terminal half of ECT2, which lacks the catalytic domain, generated cells with more than 4N DNA content, suggesting that cytokinesis was inhibited in these cells. Interestingly, ECT2-N lacking the nuclear localization signals inhibited cytokinesis more strongly than the derivatives containing these signals. Mutational analyses revealed that the XRCC1, CLB6, and BRCT domains in ECT2-N are all essential for the cytokinesis inhibition by ECT2-N. These results suggest that the XRCC1, CLB6, and BRCT domains of ECT2 play a critical role in regulating cytokinesis. Published 2003 Wiley-Liss, Inc. [source] An Insight to Pituitary Folliculo-Stellate CellsJOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2008S. Devnath Folliculo-stellate cells (FS-cells) are star-shaped and follicle-forming cells in the anterior pituitary gland that were first identified by electron microscopy as non-endocrine agranular cells. Light microscopy has revealed many of their cytophysiological features and the FS-cell is known to be positive for S-100 protein, a marker for FS-cells. So far, functions ascribed to FS-cells include the formation of an extensive and complex tridimentional network, scavenger activity by engulfing degenerated cells, paracrine regulation of endocrine cells by producing various growth factors and cytokines, such as interleukin-6, leukemia inhibitory factor, basic fibroblastic growth factor, vascular endothelial cell growth factor and follistatin, and large-scale inter-cellular communication by means of their long cytoplasmic processes and gap junctions. Moreover, their multi-potential characteristics and other cytological features support the possibility of them becoming organ-specific stem cells. This concept is yet to be resolved, however. In this review, we focus on these features of FS-cells along with some futuristic approaches. [source] Human bone marrow stromal cell cultures conditioned by traumatic brain tissue extracts: Growth factor productionJOURNAL OF NEUROSCIENCE RESEARCH, Issue 5 2002Xiaoguang Chen Abstract Treatment of traumatic brain injury (TBI) with bone marrow stromal cells (MSCs) improves functional outcome in the rat. However, the specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Currently, the ability of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue appears limited at best. Tissue replacement, however, is not the only possible compensatory avenue in cell transplantation therapy. Various growth factors have been shown to mediate the repair and replacement of damaged tissue, so trophic support provided by transplanted MSCs may play a role in the treatment of damaged tissue. We therefore investigated the temporal profile of various growth factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of rat brain in vitro and quantitative sandwich enzyme-linked immunosorbent assays (ELISAs) were performed. TBI-conditioned hMSCs cultures demonstrated a time-dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive production of these growth factors by the hMSCs. The ELISA data suggest that transplanted hMSCs may provide therapeutic benefit via a responsive secretion of an array of growth factors that can foster neuroprotection and angiogenesis. © 2002 Wiley-Liss, Inc. [source] Electrostatic binding of nanoparticles to mesenchymal stem cells via high molecular weight polyelectrolyte chainsJOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 4 2009Boon C. Heng Abstract Combining stem cell transplantation with nanoparticle-mediated delivery of drugs and pharmaceuticals is envisioned to be one of the next major developmental steps in regenerative medicine. However, a major challenge would be to keep nanoparticles co-localized with stem cells upon transplantation or transfusion in situ. Since nanoparticles are physically much smaller in size than cells and would not specifically bind to extracellular matrix, it is easier for them to disperse from the transplantation site via the blood circulation. Conjugating nanoparticles directly to the cell membrane can potentially interfere with cellular function by physically obstructing cell surface receptors from interacting with the extracellular matrix, various growth factors and cytokines and other cells. Moreover, drug-loaded nanoparticles may be internalized into the cytoplasm via endocytosis or phagocytosis, which may wreak damage on the cellular machinery, leading to impaired physiological function or cell death. A novel solution may be to utilize high molecular weight polyelectrolyte chains to electrostatically bind nanoparticles to cells. For this purpose, hyaluronan, poly- L -lysine and chitosan are of special interest, because these molecules are generally recognized to be biocompatible for application in various pharmaceutical and surgical products. This study investigated the use of these molecules to bind nanoparticles to mesenchymal stem cells (MSCs), and a novel technique of conjugating half the cell surface with nanoparticles through the use of polyelectrolyte chains was also developed. This would avoid blocking MSC interaction with cytokines, growth factors, extracellular matrix and other cells within the recipient tissue/organ upon delivery in situ. Copyright © 2009 John Wiley & Sons, Ltd. [source] Coexpression of heparanase, basic fibroblast growth factor and vascular endothelial growth factor in human esophageal carcinomasPATHOLOGY INTERNATIONAL, Issue 8 2004Shuji Mikami Heparan sulfate (HS), which is degraded by heparanase, plays an important role in cell adhesion, insolubility of the extracellular matrix (ECM) and as a reservoir for various growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). In the present study, we examined the immunohistochemical expression of heparanase, bFGF and VEGF, and evaluated the correlation between their expression and microvessel density (MVD) in human esophageal carcinomas. Heparanase, bFGF and VEGF were immunolocalized predominantly to the carcinoma cells, but they were also localized to the endothelial cells of microvessels near the carcinoma cell nests. In carcinomas with invasion of the muscular layer or adventitia, heparanase staining was stronger at the invasive areas of carcinomas than the intraepithelial spread. Expression of heparanase and bFGF and the degree of MVD were associated, with, tumor, invasion,, lymph, node, metastasis, and pathological stages. Cases with positive staining for heparanase, bFGF or VEGF tended to have a higher MVD than those without staining, and carcinomas with concomitant expression of heparanase, bFGF and VEGF showed the highest MVD. The level of heparanase mRNA expression was directly correlated with the MVD. In addition, heparanase-positive cases had a higher positive ratio of bFGF and VEGF compared with the heparanase-negative cases. These data suggest the possibility that heparanase may contribute to not only cancer cell invasion but also angiogenesis probably through degradation of HS in the ECM and release of bFGF and VEGF from the HS-containing ECM. [source] Epithelial differentiation of adipose-derived stem cells for laryngeal tissue engineering,THE LARYNGOSCOPE, Issue 1 2010Jennifer L. Long MD Abstract Objectives/Hypothesis: One potential treatment option for severe vocal fold scarring is to replace the vocal fold cover layer with a tissue-engineered structure containing autologous cells. As a first step toward that goal, we sought to develop a three-dimensional cell-populated matrix resembling the vocal fold layers of lamina propria and epithelium. Study Design: Basic science investigation. Methods: Adipose-derived stem cells were cultured in fibrin hydrogels with various growth factors. At the end of the culture period, matrices were sectioned and labeled with immunomarkers to identify cell phenotype. Results: Adipose-derived stem cells survived, attached, and populated three-dimensional fibrin matrices. Under select conditions, a superficial layer of cells expressing epithelial marker proteins overlay a deeper mesenchymal cell layer. Conclusions: A three-dimensional structure of fibrin and adipose-derived stem cells was created as a prototype vocal fold replacement. Two segregated cell phenotypes occurred, producing a bilayered structure resembling epithelium over lamina propria. This preliminary work demonstrates the feasibility of tissue engineering to produce structures for vocal fold replacement. Laryngoscope, 2010 [source] NF-,B activation in development and progression of cancerCANCER SCIENCE, Issue 3 2007Jun-ichiro Inoue Nuclear factor-,, (NF-,B) binds specifically to NF-,B-binding sites (,B sites, 5,-GGGRNNYYCC-3,; R, purine; Y, pyrimidine; N, any nucleotide) present in enhancer regions of various genes. Binding of various cytokines, growth factors and pathogen-associated molecular patterns to specific receptors activates NF-,B and expression of genes that play critical roles in inflammation, innate and acquired immunity, bone remodeling and generation of skin appendices. Activation of NF-,B is also involved in cancer development and progression. NF-,B is activated in cells that become malignant tumors and in cells that are recruited to and constitute the tumor microenvironment. In the latter scenario, the TLR-TRAF6-NF-kB pathways seem to play major roles, and NF-,B activation results in production of cytokines, which in turn induce NF-,B activation in premalignant cells, leading to expression of genes involved abnormal growth and malignancy. Furthermore, NF-,B activation is involved in bone metastasis. Osteoclasts, whose generation requires the RANK-TRAF6-NF-,B pathways, release various growth factors stored in bone, which results in creation of microenvironment suitable for proliferation and colonization of cancer cells. Therefore, NF-,B and molecules involved its activation, such as TRAF6, are attractive targets for therapeutic strategies against cancer. (Cancer Sci 2007; 98: 268,274) [source] Vernal keratoconjunctivitis: a major reviewACTA OPHTHALMOLOGICA, Issue 2 2009Sunil Kumar Abstract. Vernal keratoconjunctivitis (VKC) is a chronic, bilateral, at times asymmetrical, seasonally exacerbated, allergic inflammation of the ocular surface, involving tarsal and/or bulbar conjunctiva. Though the allergic nature of this entity has been accepted for a long time, the accumulation of a large amount of immunological data has proved that the pathogenesis of VKC is much more complex than a mere type 1 hypersensitivity reaction. In the past several years, many clinical and experimental studies about the cells and mediators involved in initiating and perpetuating the ocular allergic inflammation have shown that T helper type 2 cells and their cytokines, corneal fibroblasts and epithelium along with various growth factors play an important role in the pathogenesis of VKC. Based on this information about the pathogenesis of VKC newer, more selective drugs like anti-chemokine receptor antibodies and leukotriene receptor antagonists are under evaluation. Cyclosporine has been shown to be effective in the treatment of VKC but further randomized control trials are required to establish the minimum effective concentration. [source] | |||||||||||||