Rat ES cells were derived using 3I medium from E4.5 blastocysts. Rat embryonic fibroblast cells were derived form E14.5 embryos. To analyze the mechanism under the selfrenewal of rat ES cells, microarrays were used for the genome wide analysis of gene expressoin profiles in rat ES cells. Rat embryonic fibroblast cells and mouse ES cells were tested at same time as control. Our results from clustering analysis demonstrated that the gene expression profile of rat ES cells resembles mouse ES cells, but not REFs. Keyword: 3I medium; rat embryonic stem cells; mouse ES cells; rat embryonic fibroblast cells Rat ES cells were cultured in 3I medium; rat embryonic fibroblast cells were derived and cultured GMEM/10% FBS; mouse ES cells (C57/BL6)were cultured in GMEM/10% FBS added LIF and feeder cells were removed before RNA extraction. Three replicates each.
Murine studies have shown that immunologic targeting of the tumor vasculature, a key element of the tumor stroma, can lead to protective immunity in the absence of significant pathology. In the current study, we expand the scope of stroma-targeted immunotherapy to antigens expressed in tumor-associated fibroblasts, the predominant component of the stroma in most types of cancer. Mice were immunized against fibroblast activation protein (FAP), a product up-regulated in tumor-associated fibroblasts, using dendritic cells transfected with FAP mRNA. Using melanoma, carcinoma, and lymphoma models, we show that tumor growth was inhibited in tumor-bearing mice vaccinated against FAP and that the magnitude of the antitumor response was comparable to that of vaccination against tumor cell-expressed antigens. Both s.c. implanted tumors and lung metastases were susceptible to anti-FAP immunotherapy. The antitumor response could be further enhanced by augmenting the CD4+ T-cell arm of the anti-FAP immune ...
It is well accepted that there is an increase in the number of fibroblasts in the airways of patients with asthma that correlates with thickness of lamina reticularis and disease severity. Moreover, fibroblast activation and differentiation to myofibroblasts are also evident [1-4].. In the present study, we aimed to investigate the in vitro effect of glucocorticosteroids and short-acting β2-agonists widely used as first-line antiasthmatic drugs on human lung fibroblast proliferation and IL-6 production. We specifically choose to evaluate fibroblast proliferation because this is the first hallmark of fibrosis taking place. IL-6 was selected among a plethora of proinflammatory profibrotic cytokines produced by the fibroblast[22] that mainly influences the inflammatory response [23, 24].. We found that dexamethasone and salbutamol alone and in combination increase both human fetal lung and human bronchial fibroblast proliferation. Moreover, we demonstrate for the first time that when the ...
TY - JOUR. T1 - PFG acted as an inducer of premature senescence in TIG-1 normal diploid fibroblast and an inhibitor of mitosis in the HeLa cells. AU - Huang, Ying. AU - Ohno, Osamu. AU - Miyamoto, Kenji. PY - 2019/6/1. Y1 - 2019/6/1. N2 - Our previous work has reported an anti-proliferative compound from moutan cortex, paeoniflorigenone which can induce cancer-selective apoptosis. However, its anti-proliferative mechanism is still unknown. According to morphology changes (hypertrophy and flattening), we hypothesized that PFG can induce senescence or inhibit cell mitosis. Here we show that PFG can induce cellular senescence, evidenced by the expression of senescence-associated β-galactosidase, G0/G1 cell cycle arrest and permanent loss of proliferative ability, in normal TIG-1 diploid fibroblast but not cancerous HeLa cells. In cancerous HeLa cells, PFG inhibited proliferation by inducing S and G2/M cell cycle arrest and mitosis inhibition. DNA damage response was activated by PFG, interestingly ...
Fibroblasts play important roles in several cancers. It was hypothesized that cholangiocarcinoma (CCA)-associated fibroblasts (Cfs) differ from non-tumorigenic liver fibroblasts (Lfs) in their gene expression profiles resulting in the capability to promote cancer. Periostin (PN) is a multi-functional protein and has emerged as a promising marker for tumor progression. The role of PN in CCA, however, has not yet been explored. In this study, the gene expression profile of Cfs in comparison to Lfs was performed using oligonucleotide microarrays. The common- and unique-expressed genes in Cfs and the promising roles in cancer promotion and progression were determined. PN was markedly over-expressed in Cfs confirmed by real time RT-PCR and western blot analysis. Immunohistochemistry examination of a number of patients with intrahepatic CCA showed the expression of PN solely in stromal fibroblasts, but was expressed neither in cancer cells nor immune cells. Low to no expression of PN was observed in tissues
In our laboratory, recent single cell electrophysiologic studies have demonstrated the absence of voltage-gated Ca2+ channels in human cardiac fibroblasts. The more positive membrane potential found in these cells suggests that Ca2+ entry occurs through a different mechanism. We hypothesized that non-voltage-gated Ca2+-permeable TRP channels are responsible for Ca2+ entry in human cardiac fibroblasts. With informed consent, right atrial biopsies were obtained from patients undergoing cardiac surgery (n=4:.3M, 1F; mean age 65±8 yrs, EF 63±5%, LVEDP 24±4 mm Hg). Fibroblasts were dissociated and cultured for 7 to 10 days. We found that TRPC1, TRPC4, TRPC6, TRPV4, TRPV5, TRPV6, TRPM4 and TRPM7 were detectable at message levels by RT-PCR. Functional expression of these channels was evaluated by patch-clamp technique. An outward rectifying current with typical I-V relation of TRPM7 was readily recorded in the fibroblasts. The averaged current density was 14.5±0.8 pA/pF (mean±SEM, n=60 from four ...
TY - JOUR. T1 - Protective effect of resveratrol against caspase 3 activation in primary mouse fibroblasts. AU - Ulakcsai, Zsófia. AU - Bagaméry, Fruzsina. AU - Vincze, István. AU - Szöko, Éva. AU - Tábi, Tamás. PY - 2015/1/1. Y1 - 2015/1/1. N2 - Aim: To study the effect of resveratrol on survival and caspase 3 activation in non-transformed cells after serum deprivation. Methods: Apoptosis was induced by serum deprivation in primary mouse embryonic fibroblasts. Caspase 3 activation and lactate dehydrogenase release were assayed as cell viability measure by using their fluorogenic substrates. The involvement of PI3K, ERK, JNK, p38, and SIRT1 signaling pathways was also examined. Results: Serum deprivation of primary fibroblasts induced significant activation of caspase 3 within 3 hours and reduced cell viability after 24 hours. Resveratrol dose-dependently prevented caspase activation and improved cell viability with 50% inhibitory concentration (IC50) = 66.3 ± 13.81 μM. It also reduced ...
TY - JOUR. T1 - Altered transcriptome signature of phenotypically normal skin fibroblasts heterozygous for CDKN2A in familial melanoma. T2 - Relevance to early intervention. AU - Fan, Meiyun. AU - Pfeffer, Susan R.. AU - Lynch, Henry T.. AU - Cassidy, Pamela. AU - Leachman, Sancy. AU - Pfeffer, Lawrence M.. AU - Kopelovich, Levy. PY - 2013. Y1 - 2013. N2 - Familial melanoma (FM) is a dominantly heritable cancer that is associated with mutations in the tumor suppressor CDKN2A/p16. In FM, a single inherited "hit" occurs in every somatic cell, enabling interrogation of cultured normal skin fibroblasts (SFs) from FM gene carriers as surrogates for the cell of tumor origin, namely the melanocyte.We compared the gene expression profile of SFs from FM individuals with two distinct CDKN2A/p16 mutations (V126D-p16 and R87P-p16) with the gene expression profile of SFs from age-matched individuals without p16 mutations and with no family history of melanoma. We show an altered transcriptome signature in ...
p,Fibroblasts play a major role in heart physiology. They are at the origin of the extracellular matrix renewal and production of various paracrine and autocrine factors. In pathological conditions, fibroblasts proliferate, migrate and differentiate into myofibroblasts leading to cardiac fibrosis. This differentiated status is associated with changes in expression profile leading to neo-expression of proteins such as ionic channels. The present study investigates further electrophysiological changes associated with fibroblast differentiation focusing on the activity of voltage-gated sodium channels in human atrial fibroblasts and myofibroblasts. Using the patch clamp technique we show that human atrial myofibroblasts display a fast inward voltage gated sodium current with a density of 13.28 ± 2.88 pA pF(-1) whereas no current was detectable in non-differentiated fibroblasts. Quantitative RT-PCR reveals a large amount of transcripts encoding the Na(v)1.5 α-subunit with a fourfold increased ...
... include: bladder, cardiac, dermal, gingival, lung-airway, prostate, scleral, uterine, and vas deferens.. Lifeline® normal Human Fibroblasts provide an ideal cell system to study wound healing, toxicology, cancer, or basic cell biology in various organs including skin, lung, bladder, and the reproductive systems. Our normal Human Fibroblasts can also be used for drug screening, drug development, and genome editing applications. Additionally, our fibroblast lines are ideal for establishing serum free human feeder layers for human embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and other cell culture applications requiring feeder layers.. Human Dermal Fibroblasts (Adult or Neonatal) and Xeno-Free Human Dermal Fibroblasts are cryopreserved as primary cells ...
Administration of selected concentrations of ebselen and N-acetyl cysteine have been proven to display an antioxidant potential based on their effect on markers of T cell integrity and function in human peripheral blood mononuclear cells and CD4+ T cell clones. Here we assessed the impact of various antioxidant concentrations on replicative aging of primary human fibroblast strains derived from embryonic lung (MRC-5) and foreskin (HFF). None of the antioxidant concentrations affected the cumulative population doublings, levels of oxidative DNA damage, intracellular GSH:GSSG ratio, potency of heat shock responses and the induction of senescence in both fibroblast strains. Our results showed no effect of both antioxidants on primary fibroblast strains and reveal their cell type specific antioxidant potential.
Human fibroblasts can express and transport both PC-I aggregates and VSVG through the Golgi complex. Human fibroblasts were stimulated to synthesize PC-I and in
Applied mechanical forces, such as those resulting from fluid flow, trigger cells to change their functional behavior or phenotype. However, there is little known about how fluid flow affects fibroblasts. The hypothesis of this thesis is that dermal fibroblasts undergo significant changes of expression of differentiation genes after exposure to fluid flow (or shear stress). To test the hypothesis, human dermal fibroblasts were exposed to laminar steady fluid flow for 20 and 40 hours and RNA was collected for microarray analysis. Gene expression data was processed using gene network analysis, pathway analysis, and gene functional analysis with comparison to data from publicly available data sets. Additional treatment with PI3K/mTOR pathway inhibitor, PI-103, was performed to evaluate pathway involvement in flow modulation of gene expression. Results from overall transcription analysis demonstrated that fluid flow modulated many genes in fibroblasts including those related to differentiation, ...
Helen There is a marker called prolyl-4-hydroxylase that is supposed to react with fibroblasts. Its from Acris cat number AF5110-1. The antibody is a mouse anti-rat. It is supposed to work in FFPE material. I just received it and have not had a change to start working on it, but I can update as soon as I start working with it. Liz Elizabeth A. Chlipala, BS, HTL(ASCP)QIHC Manager Premier Laboratory, LLC P.O. Box 18592 Boulder, Colorado 80308 Office: (303) 735-5001 Fax: (303) 735-3540 [email protected] www.premierlab.com Ship to Address: Premier Laboratory University of Colorado MCDB, Room A3B40 Boulder, Colorado 80309 -----Original Message----- From: [email protected] [mailto:[email protected]] On Behalf Of Helen Ilsley Sent: Monday, July 17, 2006 3:15 AM To: [email protected] Subject: [Histonet] fibroblast marker Hi I wonder if anyone can help me. I am looking for a fibroblast marker which can cross react with any of the following: ...
Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease for which there is no cure. Current therapeutics are only able to slow disease progression, therefore there is a need to explore alternative, novel treatment options. There is increasing evidence that the 3′, 5′ cyclic adenosine monophosphate (cAMP) pathway is an important modulator in the development of fibrosis, with increasing levels of cAMP able to inhibit cellular processes associated with IPF. In this study we investigate the expression of Gs-coupled G protein-coupled receptors (GPCR) on human lung fibroblasts (HLF), and explore which can increase cAMP levels, and are most efficacious at inhibiting proliferation and differentiation. Using TaqMan arrays we determined that fibroblasts express a range of Gs-coupled GPCR. The function of selected agonists at expressed receptors was then tested in a cAMP assay, and for their ability to inhibit fibroblast proliferation and differentiation. Expression analysis of
The importance of the tumor microenvironment on cancer growth and invasion are well appreciated (1-3), and the stiffness of the tumor stroma has been shown to drive tumorigenesis and invasion (8-10). However, in addition to matrix stiffness, interstitial flow is an important mechanical stress in the tumor stroma (5). By examining the interplay between tumor cells, fibroblasts, and interstitial flow, we showed that flow guides fibroblast invasion, leading to concurrent invasion of MDA-MB-435S tumor cells through the ECM. Without interstitial flow, fibroblasts did not affect tumor cell invasion.. TGF-β1 regulates a variety of tumor suppressive and promoting effects, including epithelial homeostasis, epithelial-to-mesenchymal transition, myofibroblast differentiation, and metastasis (36). TGF-β1 was necessary for interstitial flow-enhanced fibroblast invasion (Fig. 2A) but only indirectly involved in tumor cell invasion (Fig. 2D). We hypothesize that TGF-β1 may increase fibroblast invasion ...
TY - JOUR. T1 - c-Src enhances the spreading of src-/-fibroblasts on fibronectin by a kinase-independent mechanism. AU - Kaplan, Kenneth B.. AU - Swedlow, Jason R.. AU - Morgan, David O.. AU - Varmus, Harold E.. PY - 1995/6/15. Y1 - 1995/6/15. N2 - We have explored the role of the tyrosine kinase c-Src in cellular adhesion. Fibroblasts derived from src-/-mice (src-/-fibroblasts) exhibit a reduced rate of spreading on fibronectin. This defect is rescued by expression of wild-type chicken c-Src. Analyses of mutants suggest that c-Src increases the rate of cell spreading in src-/- fibroblasts through a kinase-independent mechanism requiring both the SH3 and SH2 domains. To further address the role of c-Src in adhesion, we examined the activity and subcellular distribution of c-Src during the adhesion of fibroblasts on fibronectin. We observed a transient increase in the specific kinase activity of c-Src accompanied by the partial dephosphorylation of the negative regulatory site Y527. Activation of ...
Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels
Identification of fibroblast derived factors in tumor progression has the potential to provide novel molecular targets for modulating tumor cell growth and metastasis. Multiple matrix metalloproteases (MMPs) are expressed by both mesenchymal and epithelial cells within head and neck squamous cell carcinomas (HNSCCs), but the relative importance of these enzymes and the cell source is the subject of controversy. The invasive potential of HNSCC tumor cells were assessed in vitro atop type I collagen gels in coculture with wild-type (WT), MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts. A floor of mouth mouse model of HNSCC was used to assess in vivo growth after co-injection of FaDu tumor cells with MMP null fibroblasts. Here we report changes in tumor phenotype when FaDu HNSCCs cells are cocultured with WT, MMP-2 null, MMP-9 null or MT1-MMP null fibroblasts in vitro and in vivo. WT, MMP-2 null and MMP-9 null fibroblasts, but not MT1-MMP null fibroblasts, spontaneously invaded into type I collagen gels
Fibroblast apoptosis is a critical component of normal repair and the acquisition of an apoptosis-resistant phenotype contributes to the pathogenesis of fibrotic repair. Fibroblasts from fibrotic lungs of humans and mice demonstrate resistance to apoptosis induced by Fas-ligand and prior studies have shown that susceptibility to apoptosis is enhanced when Fas (CD95) expression is increased in these cells. Moreover, prior work shows that Fas expression in fibrotic lung fibroblasts is reduced by epigenetic silencing of the Fas promoter. However, the mechanisms by which microenvironmental stimuli such as TGF-β1 and substrate stiffness affect fibroblast Fas expression are not well understood. Primary normal human lung fibroblasts (IMR-90) were cultured on tissue culture plastic or on polyacrylamide hydrogels with Youngs moduli to recapitulate the compliance of normal (400 Pa) or fibrotic (6400 Pa) lung tissue and treated with or without TGF-β1 (10 ng/mL) in the presence or absence of protein kinase
Wound healing is a complex process that requires an interplay between several cell types. Classically, fibroblasts have been viewed as producers of extracellular matrix, but more recently they have been recognized as orchestrators of the healing response, promoting and directing, inflammation and neovascularization processes. Compared to those from healthy tissue, inflammation-associated fibroblasts display a dramatically altered phenotype and have been described as sentinel cells, able to switch to an immunoregulatory profile on cue. However, the activation mechanism still remains largely uncharacterized. Nemosis is a model for stromal fibroblast activation. When normal human primary fibroblasts are deprived of growth support they cluster, forming multicellular spheroids. Clustering results in upregulation of proinflammatory markers such as cyclooxygenase-2 and secretion of prostaglandins, proteinases, cytokines, and growth factors. Fibroblasts in nemosis induce wound healing and tumorigenic ...
Cardiac fibrosis is a major component of heart disease and is a hallmark of decreased cardiac function. Currently, there are no treatments that attenuate fibrosis directly. This major hurdle can be overcome by targeting the resident fibroblast. Preliminary data demonstrates that loss of PDGFRα expression in the adult cardiac fibroblast lineage results in loss of over half of resident fibroblasts. A time course experiment revealed that in as little as 4 days after PDGFRα gene deletion fibroblast loss can observed. Based on the basal level of fibroblast proliferation (0.8%+/-0.9, i.e. 4 of 398 cells), we hypothesize that PDGFRα signaling is essential for fibroblast maintenance and that fibroblasts undergo rapid turnover. We have begun to elucidate which downstream signals of PDGFRα are involved the different roles of the fibroblast. Using a PDGFRα-dependent-PI3K-deficient mouse model, preliminary data indicates that PDGFRα-dependent PI3K signaling is involved in this cell survival response. ...
Cancer-associated fibroblasts (CAF) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLCs, a cross-species functional characterization of mouse and human lung CAFs was conducted. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in patients with NSCLC. This secreted gene signature was upregulated in normal lung fibroblasts after long-term exposure to tumor cells, showing that lung fibroblasts are ...
Chronic kidney disease (CKD) is a global socioeconomic problem. It is characterised by the presence of differentiated myofibroblasts that, in response to TGF B-1, produce tissue fibrosis, leading to renal failure. Here we define a novel interaction between the SET9 lysine methyltransferase and SMAD3, the principle mediator of TGF B-1 signalling in myofibroblasts. We show that SET9 deficient fibroblasts exhibit globally altered gene expression profiles in response to TGF B-1, whilst overexpression of SET9 enhances SMAD3 transcriptional activity. We also show that SET9 facilitates SMAD3 nuclear import and controls SMAD3 protein degradation, in a manner involving ubiquitination. On a cellular level, we demonstrate that SET9 is broadly required for TGF B-1 effects in diseased primary renal fibroblasts; SET9 promotes fibroblast migration into wounds, expression of extracellular matrix proteins, collagen contractility and myofibroblast differentiation. Finally, we demonstrate that SET9 is recruited to ...
We performed subtractive and differential hybridization for transcript comparison between murine fibroblasts and isogenic epithelium, and observed only a few novel intracellular genes which were relatively specific for fibroblasts. One such gene encodes a filament-associated, calcium-binding protein, fibroblast-specific protein 1 (FSP1). The promoter/enhancer region driving this gene is active in fibroblasts but not in epithelium, mesangial cells or embryonic endoderm. During development, FSP1 is first detected by in situ hybridization after day 8.5 as a postgastrulation event, and is associated with cells of mesenchymal origin or of fibroblastic phenotype. Polyclonal antiserum raised to recombinant FSP1 protein stained the cytoplasm of fibroblasts, but not epithelium. Only occasional cells stain with specific anti-FSP1 antibodies in normal parenchymal tissue. However, in kidneys fibrosing from persistent inflammation, many fibroblasts could be identified in interstitial sites of collagen ...
Survivin encoded by BIRC5 belongs to the group of proteins that inhibit apoptosis. It consists of the BIR and α-helical C domains. In addition to its inhibitory activity, it plays an important role in cell cycle regulation. Adalimumab is an immunosuppressive drug, a recombinant human anti-TNF-α monoclonal antibody. It is used in the treatment of autoimmune diseases.The aim of the study was to evaluate changes in the expression of BIRC5 and genes encoding apoptosis inhibitors (IAP), depending on the exposure time of the cells to adalimumab. The study material consisted of normal human dermal fibroblasts (NHDF) cultured under standard conditions in the presence of adalimumab (8µg/mL) for 2, 8 and 24 hours. The expression profile of genes associated with apoptosis was determined with the use of HG-U133A 2.0 oligonucleotide microarrays (Affymetrix). The comparative analysis was performed with one-way ANOVA and Tukey's HSD tests (p,0.05) using the PL-Grid Infrastructure ...
Results We observed increased expression of JMJD3 in SSc skin compared to healthy controls. Fibroblast-specific overexpression of JMJD3 was also reflected in experimental fibrosis models. TGFβ upregulated JMJD3. Inhibition of JMJD3 increased H3K27me3 in vitro and in vivo. Inhibition of JMJD3 reverted the activated fibroblast phenotype in SSc fibroblasts and decreased the expression of contractile fibers and of α-smooth muscle actin. In addition, JMJD3 inhibition reduced the basal and TGFβ induced collagen secretion of SSc fibroblasts. JMJD3 regulated the TGFβ induced expression of Fra2. GSKJ4 reverted the TGFβ induced reduction of H3K27me3 at the Fra2 promotor. Moreover, the anti-fibrotic effects of JMJD3 inhibition were evened in Fra2 knockout fibroblasts. Overexpression of Fra2 in JMJD3-knockdown fibroblasts restored the profibrotic effect of JMJD3. In vivo, inhibition of JMJD3 ameliorated fibrosis in bleomycin- and TopoI- induced experimental fibrosis and reduced dermal thickening, ...
Cancer-associated fibroblasts (CAF) remain a poorly characterized, heterogeneous cell population. Here we characterized two previously described tumor-promoting CAF sub-types, smooth muscle actin (SMA)-positive myofibroblasts and senescent fibroblasts, identifying a novel link between the two. Analysis of CAF cultured ex vivo, showed that senescent CAF are predominantly SMA-positive; this was confirmed by immunochemistry in head & neck (HNSCC) and esophageal (EAC) cancers. In vitro, we found that fibroblasts induced to senesce develop molecular, ultrastructural and contractile features typical of myofibroblasts and this is dependent on canonical TGF-β signaling. Similar to TGF-β1-generated myofibroblasts, these cells secrete soluble factors that promote tumor cell motility. However, RNA-sequencing revealed significant transcriptomic differences between the two SMA-positive CAF groups, particularly in genes associated with extracellular matrix (ECM) deposition and organization, which
Both in vivo and in vitro studies have demonstrated that fibroblasts contribute to tumor formation and growth rates (6) , and can be thought of as "contracted farmers" used by tumors to prepare the microenvironment. Fibroblasts coinoculated with breast or bladder tumor cell lines in nude mice shorten tumor latency and increase tumor growth (7) . Fibroblasts cultured from malignant tumors have stimulatory effects on MCF-7 cells, whereas fibroblasts cultured from normal tissue are inhibitory (8) . Phenotypic differences among tumor-associated fibroblasts have also been seen. Fibroblasts with smooth muscle differentiation, termed myofibroblasts, are abundant in the stromal cells of malignant breast tissue but are rarely seen in normal breast tissue (9) . These findings suggest that tumor-associated fibroblasts are functionally distinct compared with fibroblasts that are not in the tumor microenvironment, and subpopulations of fibroblast may perform specialized functions to coordinate events ...
Idiopathic pulmonary fibrosis (IPF) is a progressive, severely debilitating disease with a high mortality rate. Nintedanib (BIBF 1120) is a receptor tyrosine kinase inhibitor specific for platelet-derived growth factor receptor, fibroblast growth factor receptor and vascular endothelial growth factor receptor. Its effect on IPF disease progression measured by lung function decline has been investigated in two replicate Phase III clinical trials (INPULSIS-1 and -2) in patients with IPF. Interleukin-1 beta (IL-1β) is a potent pro-fibrotic mediator stimulating fibroblast proliferation a hallmark of IPF.. Aim: To determine the effect of nintedanib on proliferation rate of IL-1β-stimulated primary human lung fibroblasts.. Methods: Primary human lung fibroblasts from patients with IPF (IPF-HPF) and from non-fibrotic control donors (HPF) were incubated with nintedanib (1 nM - 1000 nM) for 30 min. Subsequently the cells were stimulated with IL-1β and cell proliferation was assessed by BrdU assay ...
3T3 cells come from a cell line established in 1962 by two scientists then at the Department of Pathology in the New York University School of Medicine, George Todaro and Howard Green. The 3T3 cell line has become the standard fibroblast cell line. Todaro and Green originally obtained their 3T3 cells from Swiss albino mouse embryo tissue. The 3T3 designation refers to the abbreviation of "3-day transfer, inoculum 7005300000000000000♠3×105 cells." This cell line was originally established from the primary mouse embryonic fibroblast cells that were cultured by the designated protocol, so-called 3T3 protocol. The primary mouse embryonic fibroblast cells were transferred (the "T") every 3 days (the first "3"), and inoculated at the rigid density of 7005300000000000000♠3×105 cells per 20 cm2 dish (the second "3") continuously. The spontaneously immortalized cells with stable growth rate were established after 20 to 30 generations in culture, and then named 3T3 cells. Specifically, ...
TY - JOUR. T1 - Foetal-to-adult transitions in fibroblast phenotype. T2 - their possible relevance to the pathogenesis of cancer. AU - Schor, S L. AU - Schor, A M. PY - 1987. Y1 - 1987. N2 - We have previously shown that the migration of foetal, adult and transformed fibroblasts into three-dimensional collagen gels is differentially affected by plating cell density. We now present data indicating that the migration of these fibroblasts is also differentially affected by local cell density in microdomains of the gel surface. In this article we discuss the possible biochemical and behavioural mechanisms that may contribute to the different migratory phenotypes expressed by foetal, adult and transformed fibroblasts; these include: (1) cell-induced alterations in the orientation and or packing density of collagen fibres in the gel; (2) deposition of specific matrix macromolecules by the fibroblasts; (3) social interactions between the cells; and (4) secretion of soluble factors affecting cell ...
Fibroblasts are a main player in the tumor-inhibitory microenvironment. Upon tumor initiation and progression, fibroblasts can lose their tumor-inhibitory capacity and promote tumor growth. The molecular mechanisms that underlie this switch have not been defined completely. Previously, we identified four proteins overexpressed in cancer-associated fibroblasts and linked to Rho GTPase ... read more signaling. Here, we show that knocking out the Ras homolog family member A (RhoA) gene in normal fibroblasts decreased their tumor-inhibitory capacity, as judged by neighbor suppression in vitro and accompanied by promotion of tumor growth in vivo. This also induced PC3 cancer cell motility and increased colony size in 2D cultures. RhoA knockout in fibroblasts induced vimentin intermediate filament reorganization, accompanied by reduced contractile force and increased stiffness of cells. There was also loss of wide F-actin stress fibers and large focal adhesions. In addition, we observed a significant ...
Background: Cardiac fibrosis is associated with a variety of heart diseases including atrial fibrillation (AF). Cardiac fibroblast is the major cell type in cardiac fibrogenesis cascade. However, the biological as well as electrophysiological properties of cardiac fibroblasts are not fully understood. In this study, we investigated the functional expression of voltage-gated and non-voltage-gated ion channels in artial fibroblasts from AF patients and SR patients, and their contribution to atrial fibrogenesis.. Methods: With informed consent, right atrial biopsies were obtained from AF patients or sinus rhythm (SR) patients undergoing cardiac surgery. Fibroblasts were dissociated from the biopsy samples from SR patients or AF patients. The freshly isolated cells were used for patch-clamp and ratio Ca2+-imaging experiments.. Results: We found that there are two types of voltage-gated outward potassium channels in the fibroblasts from SR patients: one is transient outward potassium current (Ito), ...
Cell lines. EBV-transformed LCLs and primary dermal fibroblasts were established as previously described (57). Previously used LCLs from an unaffected individual, AG1010 (24), termed control LCLs, were used in all experiments. In experiments with primary dermal fibroblasts, a previously used cell line from a healthy individual, 82-6 (30), termed control fibroblasts 1, was used for all experiments. To corroborate the findings in some experiments, additional cell lines from unaffected individuals (IMR-90, NHDF, and 1101-SK) were used and are termed control fibroblasts 2, 3, and 4, respectively. 88-1 normal fibroblasts were also used. Primary dermal fibroblasts were maintained in DMEM supplemented with 10% FBS. Human osteosarcoma (U2OS) and non-small-cell lung cancer (H1299) cell lines were also maintained in DMEM supplemented with 10% FBS. LCLs were maintained in RPMI medium supplemented with 10% FBS. Cell lines were obtained from Junko Oshima, Lyubomir Vassilev (Serono Research and Development ...
AppliedStemCell eCommerce Platform Human Skin Cells (Dermal Fibroblasts) (DMD) [ASE-5014] - Catalog Number ASE-5014 Quantity 5.0 x 105 cells/mL Product Information Description Human fibroblasts are derived from cultured skin explants. These fibroblasts ar
AppliedStemCell eCommerce Platform Human Skin Cells (Dermal Fibroblasts) (LCP) [ASE-5055] - Catalog Number ASE-5055 Quantity 5.0 x 105 cells/mL Product Information Description Human fibroblasts are derived from cultured skin explants. These fibroblasts ar
Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. Transforming growth factor (TGF)-β1, a mediator of fibrosis, can potentially modulate cAMP by altering PGE2 metabolism. The present study assessed whether PDE4 inhibitors functionally antagonize the profibrotic activity of fibroblasts stimulated by TGF-β1. The PDE4 inhibitors roflumilast and rolipram both inhibited fibroblast-mediated contraction of three-dimensional collagen gels and fibroblast chemotaxis toward fibronectin in the widely studied human fetal lung fibroblast strain HFL-1 and several strains of fibroblasts from adult human lung. Roflumilast was ~10-fold more potent than rolipram. There was a trend for PDE4 inhibitors to inhibit more in the presence of TGF-β1 (0.05 , P , 0.08). The ...
TY - JOUR. T1 - Expression profiles of p53-, p16INK4a-, and telomere-regulating genes in replicative senescent primary human, mouse, and chicken fibroblast cells. AU - Kim, Hyunggee. AU - You, Seungkwon. AU - Farris, James. AU - Kong, Byung Whi. AU - Christman, Shelly A.. AU - Foster, Linda K.. AU - Foster, Douglas N.. PY - 2002/9/2. Y1 - 2002/9/2. N2 - Replicative senescence is known to be an intrinsic mechanism in determining the finite life span of in vitro cultured cells. Since this process is recognized as an evolutionarily conserved mechanism from yeast to mammalian cells, we compared the senescence-associated genetic alterations in the p53, p16INK4a, and telomere regulatory pathways using replicative senescent human, mouse, and chicken fibroblast cells. Normal human diploid fibroblast (HDF; WI38) and chicken embryonic fibroblast (CEF) cells were shown to have a more extended in vitro proliferative potential than their mouse embryonic fibroblast (MEF) counterpart. In contrast to the HDF ...
Human Cardiac Fibroblast cDNA https://www.sciencepro.com.br/produtos/sc-6304 https://www.sciencepro.com.br/@@site-logo/logo-novo.png ...
אנו מתארים הליך ניסוי פשוט ומהיר ליצירת fibroblasts העיקרי מהאוזניים והזנבות של עכברים. ההליך...
Cancer-associated fibroblasts (CAFs) are one of the key determinants in the malignant progression of cancer. The subject of this research was metabolic reorganization of CAFs and their participation in collagen cross-linking process. The metabolic differences between normal fibroblasts and CAFs were elucidated using two-photon fluorescence lifetime imaging microscopy (FLIM). Collagen structure in 3D model was assessed using second harmonic generation (SHG) microscopy. We show increased metabolic activity of fibroblasts derived from patients colon tumor with a shift to more oxidative metabolism compare to dermal fibroblasts. The results of the study of collagen suggest that CAFs may contribute to the tumor progression through the facilitation of collagen alignment. In general, our findings support the idea of the strong association between cancer cells and fibroblasts and extensive involvement of CAFs in modulation of tumor microenvironment ...
Draye, JP. ; Quintart, J. ; Courtoy, Pierre J. ; Baudhuin, Pierre. Fate of I-125-labeled Plasma-membrane Polypeptides in Cultured Rat Fibroblasts - Quantification of Their Association With Lysosomes.In: Archives Internationales de Physiologie et de Biochimie, Vol. 92, no. 5, p. B131-B132 (1984 ...
SuperCult® Fibroblast Growth Medium Kit-CD is a serum-free, chemically defined medium for the growth of adult and neonatal human Dermal Fibroblast Cells. SuperCult® Fibroblast Growth Medium Kit-CD is optimized for multiple passage expansion of NHDFs. Cells can be directly transitioned from serum-containing medium to SuperCult® Fibroblast Growth Medium Kit-CD with little to no adaptation time. In addition, dermal fibroblasts grow on any culture ware and need no attachment matrix before adding SuperCult® Fibroblast Growth Medium Kit-CD ...
P. S. RUDLAND, A. E. SMITH, S. WEIL; Translational Control of Protein Synthesis after Re-initiation of the Growth of Cultured Mouse Fibroblasts. Biochem Soc Trans 1 December 1975; 3 (6): 1145-1148. doi: https://doi.org/10.1042/bst0031145. Download citation file:. ...
Objective. Synovial fibroblasts share a number of phenotype markers with fibroblasts derived from bone marrow. In this study we investigated the role of matched fibroblasts obtained from 3 different sources (bone marrow, synovium, and skin) to test the hypothesis that synovial fibroblasts share similarities with bone marrow-derived fibroblasts in terms of their ability to support survival of T cells and neutrophils. Methods. Matched synovial, bone marrow, and skin fibroblasts were established from 8 different patients with rheumatoid arthritis who were undergoing knee or hip surgery. Resting or activated fibroblasts were cocultured with either CD4 T cells or neutrophils, and the degree of leukocyte survival, apoptosis, and proliferation were measured. Results. Fibroblasts derived from all 3 sites supported increased survival of CD4 T cells, mediated principally by interferon-beta. However, synovial and bone marrow fibroblasts shared an enhanced site-specific ability to maintain CD4 T cell ...
Results 1. The proliferation of CFb is significantly promoted after adding Ang II, compared with the control group (p,0.05 or p,0.01). The 100 μg/l TP showed the effect of inhibiting the proliferation of CFb at the first 24 h (p,0.01), reached a peak within 48 h (p,0.001), started to diminish after 72 h, indicate the best time to exert effects were at 2 to 3 days. 2. With the time increase after adding Ang II, collagen synthesis increased, there is significant difference compared with the control group (p,0.05 or p,0.01). After 24 h, 48 h, 72 h of adding TP, the collagen content of each group compared with the Ang II group were significantly different. The effect of high concentration TP (100 μg/l) reached the peak (p,0.001) at 48 h (p,0.001). 3. After 24 h of adding Ang II, TGF-β1 expression was significantly increased (p,0.01). After 24 h of adding different concentrations of TP, TGF-β1 expression were significantly decreased (p,0.05 or p,0.01). 4. After 30min of adding Ang II, ERK1/2 ...
Cancer-associated fibroblasts (CAFs) support tumorigenesis by stimulating angiogenesis, cancer cell proliferation, and invasion. We demonstrate that CAFs also mediate tumor-enhancing inflammation. Using a mouse model of squamous skin carcinogenesis, we found a proinflammatory gene signature in CAFs isolated from dysplastic skin. This signature was maintained in CAFs from subsequent skin carcinomas and was evident in mammary and pancreatic tumors in mice and in cognate human cancers. The inflammatory signature was already activated in CAFs isolated from the initial hyperplastic stage in multistep skin tumorigenesis. CAFs from this pathway promoted macrophage recruitment, neovascularization, and tumor growth, activities that are abolished when NF-kappaB signaling was inhibited. Additionally, we show that normal dermal fibroblasts can be educated by carcinoma cells to express proinflammatory genes.
Randomly seeded Petri dish cultures of embryonic human lung fibroblasts generate, in the course of their growth, highly ordered cellular arrangements. Thick, bilaterally symmetrical ridges with an axial polarity and an orthogonal, multilayered internal organization are observed within stationary cultures. The generation of these structures has been investigated. Ridges result from the spontaneous aggregation of cells in postconfluent cultures brought about by directed cell movements. These movements are promoted by the localized production of extracellular matrix sheets containing collagen, which provide new substrates for cellular colonization. Cells that have colonized one matrix substrate may secrete another above themselves, which will in turn be colonized. By a continuation of this cycle, thick stacks consisting of alternate layers of cells and matrix are produced to yield the observed aggregations. The distribution and shape of ridges in a culture imply that matrix substrates are confined ...
PURPOSE:To evaluate the role of transforming growth factor beta 1 (TGF-β1) on the induced osteogenic differentiation of human dermal fibroblasts.METHODS:We performed four groups with cultured dermal fibroblasts according to the culture medium: CONTROL (DMEM culture medium); TGF-β1 (DMEM culture medium with 10 ng/ml of TGF-β1); OSTEOG (DMEM culture medium with 0.5 µg/ml of ascorbic acid, 10 mmol/l of β-glycerophosphate and 10 nmol/L of dexamethasone); and OSTEOG/TGF-β1 (osteogenic medium with 10 ng/ml of TGF-β1). Alkaline phosphatase (ALP) activity and the amount of osteocalcin (OC) in the supernatant, as well as the capability to form calcium phosphate deposits, were analysed for 28 dayRESULTS:There were significant differences (p,0.05) between CONTROL and TGF-β1 groups in comparison with OSTEOG and OSTEOG/TGF-β1 groups in the ALP activity and OC amount. Although, both osteogenic groups had the same behavior with regard the expression curve during the experimental time, the ...
Background: Transforming growth factor beta (TGFβ), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFβ on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown. Methods: We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFβ in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFβ-regulated genes. Additional criteria were an average up- or down- regulation of at least two ...
Background: Transforming growth factor beta (TGFβ), a multifunctional cytokine, plays a crucial role in the accumulation of extracellular matrix components in lung fibrosis, where lung fibroblasts are considered to play a major role. Even though the effects of TGFβ on the gene expression of several proteins have been investigated in several lung fibroblast cell lines, the global pattern of response to this cytokine in adult lung fibroblasts is still unknown. Methods: We used Affymetrix oligonucleotide microarrays U95v2, containing approximately 12,000 human genes, to study the transcriptional profile in response to a four hour treatment with TGFβ in control lung fibroblasts and in fibroblasts from patients with idiopathic and scleroderma-associated pulmonary fibrosis. A combination of the Affymetrix change algorithm (Microarray Suite 5) and of analysis of variance models was used to identify TGFβ-regulated genes. Additional criteria were an average up- or down- regulation of at least two ...
Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT ...
Fibrosis involves activation of fibroblasts, increased production of collagen and fibronectin and transdifferentiation into contractile myofibroblasts. The process resembles aspects of wound-healing but remains unresolved and can be life-threatening when manifest in the kidneys, lungs and liver, in particular. The causes are largely unknown, but recent suggestions that repetitive micro-injury results in the eventual failure of epithelial cell repair due to replicative senescence are gaining favour. This is consistent with the onset of fibrotic diseases in middle age. Because epithelial injury often involves blood loss, inflammatory responses associated with the fibrotic response have been considered as therapeutic targets. However, this has proved largely unsuccessful and focus is now switching to earlier events in the process. These include EMT (epithelial-mesenchymal transition) and fibroblast activation in the absence of inflammation. TGFβ1 (transforming growth factor-β1) induces both EMT ...
The Quantum Cell Expansion System is a functionally closed and automated hollow-fiber bioreactor system that is designed to expand both adherent and suspension cells in a reproducible manner. The hollow-fiber membrane requires a coating agent to help facilitate cellular adherence when culturing an adherent cell type such as MSCs. Pooled human cryoprecipitate (CPPT, Bonfils Blood Center) was examined as an alternative to FN because it is a rich source of extracellular matrix components, including fibrinogen (Freedman, 2010), and also because it was previously shown to help aid cellular adherence in tissue culture flasks (Nikolaychik, 1994). The first examination was a direct comparison of cell expansion when with 5 mg FN coat and a single donor equivalent from a pooled donor CPPT product, followed by an examination of different CPPT volumes needed to expand precultured MSC or bone marrow-derived MSC. Direct comparisons of FN and CPPT showed no statistical difference (p-value 0.3125) while still ...
Background Stromal fibroblasts can contribute to tumor invasion through the release of matrix metalloproteinases (MMPs). Population studies have suggested that single nucleotide polymorphisms (SNPs) in MMP genes influence levels of expression and may be associated with breast cancer risk and with disease progression. This study directly examined the impact of MMP SNP genotype on the ability of host fibroblasts to promote tumor cell invasion. Methods Primary breast fibroblasts were isolated from patients with (n = 13) or without (n = 19) breast cancer, and their ability to promote breast cancer cell invasion was measured in in vitro invasion assays. Fibroblast invasion-promoting capacity (IPC) was analyzed in relation to donor type (tumor or non-tumor patient), MMP-1, MMP-3, and MMP-9 SNP genotype and MMP activity using independent samples t test and analysis of variance. All statistical tests were two-sided. Results Tumor-derived fibroblasts promoted higher levels of invasion than normal ...
3D reconstruction of a cardiomyocyte (heart muscle cell), derived from a fibroblast via direct reprogramming. Direct reprogramming allows scientists to transform one cell type into another without first reverting back to the pluripotent, stem-cell state. Animation: Scott Metzler. "Fibroblasts make up about 50% of all cells in the heart and therefore represent a vast pool of cells that could one day be harnessed and reprogrammed to create new muscle," said Dr. Srivastava. "Our findings here serve as a proof of concept that human fibroblasts can be reprogrammed successfully into beating heart cells.". In 2012, Dr. Srivastava and his team reported in the journal Nature that fibroblasts could be reprogrammed into beating heart cells by injecting just three genes, together known as GMT, into the hearts of live mice that had been damaged by a heart attack. They reasoned that the same three genes could have the same effect on human cells. But initial experiments on human fibroblasts from three ...
Figure 8 Reprogramming of human fibroblasts. (a) Phase-contrast image and immunostaining for the indicated proteins in untreated and 4TF- treated human fibroblasts. (b) Relative mRNA expression level of the indicated genes as determined by qPCR. Error bars, s.e.m. Significant differences were assessed by Students unpaired t -test, n = 3 biologically independent samples, ∗∗∗ P , 0.001, ∗∗ P , 0.01, ∗ P , 0.05. (c) Untreated human fibroblasts and human induced renal epithelial cells (h-iRECs) cultured in 3D Matrigel. Shown are maximum intensity projections of confocal z-stacks. (d) Matrigel-grown h-iREC spheres stained for actin (phalloidin) and β-catenin. (e) Percentage of PROM1+ /EPCAM+ double-positive cells (top panel) and percentage of CDH16-GFP+ cells (bottom panel) as determined by flow cytometry. 4TF human fibroblasts were treated with SV40. (f) Heatmap of RNA-seq expression analysis in human fibroblasts (0TF), CDH16-GFP+ sorted h-iRECs (4TF) and human kidney. Differentially ...
The objective of this study was to examine the effects of heparan sulfate (HS) on factors involved in the remodeling of connective tissue observed in patients with fibrotic respiratory disorders such as asthma. A suitable working model is to stimulate human fetal lung fibroblasts in vitro with structurally different forms of HS. Highly sulfated and iduronic acid (IdoUA)-rich HS specifically decreased cell proliferaton, production of jyaluronan (HA), transforming growth factor (TGF)-β1, and TFF-β-induced α-smooth muscle actin but did not affect the overall proteoglycan production in the cells. These repressed factors are suggested to play a critical role in the early stages of remodeling and myofibroblast activation. Low sulfated and IdoUA-poor HS did not display any effects on these factors. Furthermore, analysis of the protein expression pattern by two-dimensional gel electrophoresis revealed a 70% increased expression of annexin II, which has previously been shown to have a high affinity for both
Inflammation is a beneficial host response to tissue damage. Most episodes of inflammation resolve spontaneously and do not persist. However, in rheumatoid arthritis (RA), as in a number of other chronic inflammatory diseases, the inflammatory response persists and a stable inflammatory infiltrate accumulates in the joint. What drives this persistence and the relative contribution of infiltrating leucocytes and stromal cells such as fibroblasts to the stability of the inflammatory process are the subject of this article. Fibroblasts play an important role in defining the disordered synovial microenvironment in RA. Through their production of a variety of cytokines and constitutive chemokines they directly alter the behaviour of infiltrating leucocytes, leading to their inappropriate survival and retention. These findings suggest that stromal cells such as fibroblasts play an important role in the switch from acute resolving to chronic persistent arthritis by allowing lymphocytes to accumulate in the
Fibroblasts, including Cardiac Fibroblasts, & other primary cells at Cell Applications, your worldwide provider of human & animal cells, antibodies, & cell culture & molecular biology tools.
ZenBio Human Dermal Fibroblasts Biological Products. Dermal Fibroblasts are available from donors with and without Type 2 diabetes.
It has been hypothesized that chronic inflammatory diseases such as rheumatoid arthritis (RA) may be caused by a failure of negative feedback mechanisms. This study sought to examine negative feedback mechanisms in fibroblast-like synoviocytes (FLS), one of the most abundant cell types in the joint. We hypothesized that prior exposure of healthy FLS to an inflammatory stimulus would attenuate their responses to a second inflammatory stimulus, in the same way that negative feedback mechanisms desensitize macrophages to repeated stimulation by lipopolysaccharide. We further hypothesized that such negative feedback mechanisms would be defective in FLS derived from the joints in RA. Synovial fibroblasts and dermal fibroblasts from non-inflamed joints and joints affected by RA and a fibroblast cell line from neonatal foreskin were stimulated twice with tumour necrosis factor (TNF) α or interleukin (IL)-1α, with a 24-h rest period between the two 24-h stimulations. Differences between response to the first
Wrinkles at the eyes and eyelids, neck tightening, wrinkle reduction at the mouth, and stretch marks on your limbs can all be treated through fibroblast treatments. But what is fibroblast plasma therapy and what are the side effects? How much does it cost and what can it help you with versus other treatments?. Below are some facts and answers to frequently asked questions about fibroblast treatments.. How Does Fibroblast Therapy Work?. Fibroblast therapy is a non-invasive, non-surgical treatment for skin tightening and wrinkle reduction. It doesnt require an anesthesia and draws no blood. Virtually, the procedure is painless and only requires a micro-millimeter incision through which the plasma flash is applied. Virtually, the procedure leaves no marks and causes no lasting pain for you.. Are There Side Effects? Side effects with this therapy are rare but they do exist. Theyre also tend to not last nearly as long as other treatments. There can be some temporary skin irritation or ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Results Rheumatoid fibroblasts increased PBL recruitment in a disease duration-dependent manner (early RA ,newly established ,established, replacement). However, similar levels of binding were observed when fibroblasts from resolving or early RA tissue were incorporated. These data indicate that early RA and established, replacement fibroblasts have distinct phenotypes, where fibroblast in early RA have yet to acquire the ability to stimulate recruitment. When exogenous cytokines were added, co-cultures incorporating fibroblasts from resolving tissues suppressed PBL recruitment in an IL-6 and TGF-b dependent manner. Interestingly this immunosuppressive effect was lost in early RA, indicating that these fibroblasts lose their immunosuppressive phenotype early in disease development. Moreover, the mode of action of IL-6 and TGFb are hijacked in early RA, such that they no long suppress recruitment supporting aberrant lymphocyte infiltration.. ...
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The receptors for insulin and the insulin-like growth factor (IGF) I are two structurally homologous disulfide-linked multisubunit complexes of apparent Mr = 350,000. The similar subunit structures of these two types of receptors suggested that their genetic expression might be affected by common genetic defects. We have examined this possibility in an insulinresistant, diabetic patient who exhibits decreased insulin binding activity. The receptors for IGF-I and insulin in skin fibroblasts from this patient were affinity labeled with 125I-IGF-I and 125I-insulin, respectively, and visualized by electrophoresis and autoradiography in polyacrylamide gels. Control fibroblasts exhibited the usual affinity labeling of the disulfide-linked Mr = 350,000 insulin and IGF-I receptor structures.. The intensity of labeling of both receptor types in the patients fibroblasts was less than in control fibroblasts. Binding data indicated that this decrease is due to a decreased receptor number with little or no ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Fibroblasts synthesize the extracellular matrix of connective tissue and play an essential role in maintaining the structural integrity of most tissues. Researchers have long suspected that fibroblasts exhibit functional specialization according to their organ of origin, body site, and spatial location. In recent years, a number of approaches have revealed the existence of fibroblast subtypes in mice. Here, we discuss fibroblast heterogeneity with a focus on the mammalian dermis, which has proven an accessible and tractable system for the dissection of these relationships. We begin by considering differences in fibroblast identity according to anatomical site of origin. Subsequently, we discuss new results relating to the existence of multiple fibroblast subtypes within the mouse dermis. We consider the developmental origin of fibroblasts and how this influences heterogeneity and lineage restriction. We discuss the mechanisms by which fibroblast heterogeneity arises, including intrinsic ...
Results The appearance of cells with fibroblast morphology was first noted at 48 hours, and almost all cells in culture had fibroblast morphology at 96 hours. Putative fibroblasts stained for vimentin, but not for smooth muscle actin, von Willebrand factor, or cytokeratins. Cell morphology was consistent with that of fibroblasts and showed no features of epithelial, endothelial, or smooth muscle cells. Liver fibroblasts expressed procollagen-1 mRNA. ...
Stem cell research has been marked by several technical and ethical difficulties. There has been both an ethical debate and legal battle over the type of stem cells that should be used in human research. Part of the legal battle has centered on the origin of stem cells, with several legal barriers being established for the use of embryonic stem cells. Alternative methods of obtaining pluripotent stem cells have been sought and there have been several recent advancements in this effort. Researchers, lead by Dr. Asa Abeliovich from Columbia University in New York City, have successfully directed the conversion of human skin fibroblasts into functional neurons. The results of their research were published online in the journal Cell. The researchers used a lentivirus vector to transduce the fibroblasts from familial Alzheimers disease patients or unaffected individuals with the transcription-regulating genes Ascl1, Bm2, Zic1, and Myt1. In addition to the transduction process, the researchers used ...
TGF-beta has the ability to transform rat fibroblasts, but it also induces neigbouring normal cells to eliminate newly arizing transformed cells. Therefore, the transforming effect of TGF-beta can only be demonstrated when it is added to rat fibroblasts sparsely seeded in soft agar. Combination of monolayer and soft agar cultures revealed the unexpected result that transformation of rat fibroblasts by TGF-beta acts on a distinct subpopulation rather than reaching the total population. As a consequence, the comparison of transformed cells with the parental untransformed random cell population is not adequate to define alterations acquired during the transformation process ...
TY - JOUR. T1 - Mouse embryonic fibroblasts null for the Krüppel-like factor 4 gene are genetically unstable. AU - Hagos, E. G.. AU - Ghaleb, A. M.. AU - Dalton, William. AU - Bialkowska, A. B.. AU - Yang, V. W.. PY - 2009/3/5. Y1 - 2009/3/5. N2 - Krüppel-like factor 4 (KLF4) is a zinc-finger transcription factor with tumor suppressive activity in colorectal cancer. Here, we investigated whether KLF4 is involved in maintaining genetic stability in mouse embryonic fibroblasts (MEFs) isolated from mice wild type (+/+), heterozygous (+/-), or homozygous (-/-) for the Klf4 alleles. Compared to Klf4+/+ and Klf4+/- MEFs, Klf4-/- MEFs had both a higher level of apoptosis and rate of proliferation. Quantification of chromosome numbers showed that Klf4-/- MEFs were aneuploid. A higher number of Klf4 -/- MEFs exhibited γ-H2AX foci and had higher amounts of γ-H2AX compared to controls. Cytogenetic analysis demonstrated the presence of numerous chromosome aberrations including dicentric chromosomes, ...
Human Fibroblast iPC Derived Differentiated Cell Culture (Non-Viral) Media with Serum.. This product is also available without Serum Cat# M936041-01D. This product would require pre-coated flasks with Human Fibroblast iPC Derived Differentiated Cell Culture (Non-Viral) Extra-cellular Differentiation Matrix Cat# D936041-01 and Human Fibroblast iPC Derived Differentiated Cell Culture (Non-Viral) Cat# 936041-01. This product is tissue culture tested including Stem Cells and is available as 500ml sterile filtered unit.. The product is also available as a pack of 6, 500ml unit sizes.. ...
A major pathophysiological component of cardiac remodeling during heart failure (HF), cardiac fibrosis has become a target for therapeutic intervention. Additionally, compelling evidence indicates a key role of cardiac fibrosis in myocardial malfunctioning during aging. Cardiac fibrosis is a complex phenomenon resulting from aberrant activation of various cell types and signaling pathways as a consequence of injury or damage to tissue. It develops over a time course that also depends upon the type of noxa activation of tissue-specific repair programs, resulting in the subsequent activation of proliferation and migration of fibroblasts from different myocardial locations to the injury site, where they synthesize extracellular matrix (ECM) (1,2).. Tissue repair through the synthesis of new ECM by fibroblasts is beneficial, particularly after myocardial infarction. However, prolonged activation of this process results in excess scar tissue formation, increased ECM deposition, and therefore, "bad ...
Ribosomal RNA(rRNA) persists for several days estimates for rRNA half-life in vitro range from ,3 days (human fibroblasts) (primary source), through 3.8 days (18S rRNA moiety in H1299 cells) (3), to about 7.5 days (cultured rat fibroblasts) (4 ...
The CCD-11Lu human lung fibroblast cell line was used as an in vitro model. Cells were pretreated with CAPE followed by stimulation with interleukin-4 and tumor necrosis factor alpha. The levels of eotaxin in cultured supernatants were measured by enzyme-linked immunosorbent assay. The amounts of STAT6 and phosphorylated STAT6 in cellular nuclear protein extracts were determined by Western blot analysis. STAT6 DNA binding activities were detected by electrophoretic mobility shift assay. ...
Epithelial-mesenchymal interactions play a critical role in development and cancer progression. In addition to the mesenchymal cell regulation of germ layers during organogenesis, tissue fibroblasts regulate the proliferation and differentiation of epithelial tissues (1, 2). Transformed stroma can induce malignancy in lung and mammary epithelia (3, 4), and conversely, normal fibroblasts have been reported to convert malignant epithelia in the prostate and skin to morphologically benign lesions (5, 6). Known mediators of epithelial-mesenchymal interaction include members of the TGF-β family (7-9). This family is responsible for context-dependent inhibition or stimulation of cell proliferation and neoplastic transformation (10-12). TGF-β exerts its effect by binding the TGF-β type II receptor (TβRII) and subsequently recruiting the type I receptor (TβRI) for downstream cytoplasmic signaling through multiple parallel signaling pathways, including the Smad proteins (13).. To study the role of ...
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ATCC hTERT immortalized skin fibroblasts have an extended lifespan, express PDGFR(beta) and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
ATCC hTERT immortalized skin fibroblasts have an extended lifespan, express PDGFR(beta) and are karyotypically, morphologically, and phenotypically similar to the primary parent cells.
Electrical stimulation (ES) in its various forms has been shown to promote wound healing by increasing the migration of keratinocytes and macrophages, enhancing angiogenesis and stimulating dermal fibroblasts. Delivery of ES to the wound can be through biocompatible conductive biomaterials such as conductive membranes made of 5% polypyrrole (PPy) and 95% polylactide (PLA), as well as an electronic system that enables cells to be cultured on the surface of the conductors and then electrically stimulated. One of the key cells in wound healing is fibroblast contributing to extracellular matrix synthesis and interaction with epidermal cells thus contributing to wound closure. Fibroblast activities during wound healing were reported to be modulated by multiple agents including ES. However, the underline molecular mechanisms are not clear and the approach to apply electrically activated fibroblasts to assist skin wound healing needs to be explored. With this conference, we will be presenting cell ...
Im interested in transient transfection of primary mouse embryo fibroblasts. Does anyone have any experience with this and what are the best methods/protocols for high transfection efficiency (,40%)? Rizwan ...
In the present study, we confirmed that sera of patients with metastatic cancer contain tumorigenesis-signaling factors that, once delivered to recipient target cells, are capable to complete the cascade of events that eventually lead the cells to acquire malignant traits. In our previous research we had used the HEK293 cells as a model of "initiated" cell to demonstrate that the horizontal transfer of blood-circulating cancer factors is also applicable to human cells [26], confirming thus, the validity of the "genometastatic" theory in humans [23-25]. According to this theory, carcinogenetic steps such as initiation, promotion and progression might not represent events limited to the cells forming the primary tumor, but may actually be a process reproducible through cancer factors, shed by primary tumors and carried through the blood, to susceptible cells, located at metastatic sites [5, 7, 10-16]. In order to strengthen the validity of this alternative metastatic pathway in humans, we used ...
The main function of fibroblasts is to maintain the structural integrity of connective tissue by continuously secreting precursors of the…
The main function of fibroblasts is to maintain the structural integrity of connective tissue by continuously secreting precursors of the…
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
ROYAN INTERNATIONAL TWIN CONGRESS,2014. Effect of Umbilical Cord Blood Derived Platelet-lysate on Fibroblast Proliferation and Activation of Smad Signaling Pathway. Mahmoodi.M (M.Sc.) 1,2 , Ebrahimi .M (Ph.D.) 1,2 , Slideshow 6264691 by deborah-mcintosh
Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by 2 genes, GSK3A and GSK3B. GSK-3 is thought to be involved in tissue repair and fibrogenesis, but its role in these processes is currently unknown. To investigate the function of GSK-3β in fibroblasts, we generated mice harboring a fibroblast-specific deletion of Gsk3b and evaluated their wound-healing and fibrogenic responses. We have shown that Gsk3b-conditional-KO mice (Gsk3b-CKO mice) exhibited accelerated wound closure, increased fibrogenesis, and excessive scarring compared with control mice. In addition, Gsk3b-CKO mice showed elevated collagen production, decreased cell apoptosis, elevated levels of profibrotic α-SMA, and increased myofibroblast formation during wound healing. In cultured Gsk3b-CKO fibroblasts, adhesion, spreading, migration, and contraction were enhanced. Both Gsk3b-CKO mice and fibroblasts showed elevated expression and production of endothelin-1 ...
Inserting a reporter into the genome - posted in Molecular Biology: Hi all. I want to insert a GFP reporter behind the promoter of a protein of interest such that if that certain gene is expressed then GFP will be translated as well. I want to do this in a primary human fibroblast cell line. I dont know much about manipulating mammalian genomes, but how difficult would it be to do what Im describing? Do you know the time scale and how much troubleshooting/headache it would be...
Rationale: Fibroblasts exhibit an extraordinary capacity to undergo phenotypic changes during development and disease, both in vitro and in vivo. These changes include altered motility, migration or activation. Enhanced migratory capacity of primary lung fibroblasts (lfs) in IPF patients was found in vitro, but the underlying mechanisms remain elusive. The aim of this study was to decipher morphological, molecular and functional differences between invading (i) and non-invading (n-i) lfs in 3D cell culture models.. Methods/Results: We established a high-content 3D invasion model, enabling the separation of i from n-i lfs that allows the comparative analysis of parameters like morphology, invasion depth and protein/mRNA expression levels. Analysis revealed two significantly distinct subtypes. 7.62 % of untreated lfs invaded the collagen matrix. Invasion was augmented by TGFβ1 and EGF treatment. Gene expression analysis of i vs n-i lfs demonstrated significantly different expression profiles. ...
Previously scientists at Allele Biotech have reported near uniform conversion of human fibroblasts using our proprietary mRNA mixtures. The first picture below shows a well of cells after 7 days of growing fibroblasts with the new Allele mRNA mix.. This month, by adjusting the mRNA dose while testing Alleles own reprogramming medium formulation, we observed various stages of cells going through the transition in the same well (see pictures 2 to 5). All stages of reprogramming typically observed over a span of weeks can actually be seen within 1 well of a 6-well plate when we treated human fibroblasts at half the dose of our standard mRNA mix, on day 10, and using Allele Biotechs new formulation of reprogramming medium.. (1) Warren, Ni, Wang, and Guo 2012 (pdf download). ...