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At least 235 records · Page 13Linked to original sources
PubMed1999

Transplanted fetal fibroblasts: survival and distribution over time in normal adult dermis compared with autogenic, allogenic, and xenogenic adult fibroblasts.

Cell therapy is a widely applicable therapeutic approach using cells and cell elements, frequently from fetal or young animals, for their beneficial effects. This study evaluated the host response to and tolerance of transplanted fetal skin fibroblasts. Cultured fibroblasts from adult rabbit skin (autogenic and allogenic), 21-day fetal rabbit skin (allogenic), and adult pig skin (xenogenic) were labeled with a fluorescent vital dye CM-DiI, injected intradermally into the dorsal skin of adult rabbits at multiple sites and then biopsied over an 8-week period. Each cell type showed a biphasic distribution curve with an early phase (0 to 28 days) and a late phase (28 to 56 days). In the early phase, cells showed a rise and fall in total cell density (reflecting an increase and then a decrease in total cell number), followed by a slow decrease in cell density with cells still detectable at 56 days. Fetal cells showed the highest survival at the end of the study. None of the groups showed clinical or histologic signs of acute inflammation or rejection. This study demonstrated that (1) transplanted fibroblasts are well tolerated by an immunologically competent host, (2) CM-DiI-labeled cells are detectable in vivo for at least 8 weeks, and (3) fetal fibroblasts have a distribution and survival profile that is distinct from that of adult fibroblasts.

Age Factors↗
PubMed1998

Cell density-dependent regulation of fibronectin splicing at the EDA region in fibroblasts: cell density also modulates the responses of fibroblasts to TGF-beta and cancer cell-conditioned medium.

Recently we reported that cancer cell-fibroblast interactions can modulate the expression of fibronectin (FN) isoforms in vitro, i.e. conditioned medium of human rectal adenocarcinoma cell line RCM-1 (RCM-1 CM) stimulated the expression of EDA-containing FN (EDA(+)FN) mRNA by fibroblasts and this stimulation was partly mediated by transforming growth factor-beta (TGF-beta) included in RCM-1 CM. In the present study, cell density was shown to regulate FN splicing at the EDA region in fibroblasts. Fibroblasts plated at a low cell density expressed a significantly higher percentage of EDA(+)FN mRNA than those plated at a high cell density. Moreover, fibroblast cell density modulated the effects of TGF-beta and RCM-1 CM on FN splicing at the EDA region differently. The time courses of their effects were similar to each other at a high cell density. At a low cell density, however, they were different. TGF-beta showed a relatively short-lived stimulation of EDA(+)FN mRNA, with the peak response 24 h after treatment, followed by a decline to the base line by 72 h. On the other hand, RCM-1 CM caused a prolonged stimulation, maintaining almost the maximum responses from 24 to 72 h. Thus, these results at a low cell density indicated the presence of a factor(s) other than TGF-beta in RCM-1 CM that stimulates the expression of EDA(+)FN mRNA directly or modulates the effect of TGF-beta. The use of several different cell densities might help in the search for new factors affecting FN splicing.

Adenocarcinoma↗
PubMed2002

Expression of integrins by human periodontal ligament and gingival fibroblasts and their involvement in fibroblast adhesion to enamel matrix-derived proteins.

We showed recently that human periodontal ligament (PDL) and gingival fibroblasts adhere and spread on enamel matrix protein (EMP) coatings. In the present study, we investigated whether this interaction can be attributed to integrin expression. Human PDL and gingival fibroblasts were cultured for periods up to 24 h on EMP coatings, in the presence of synthetic RGD-containing peptide or an antibody against the beta1 integrin subunit. The cells were first cultured for 24 h under serum-free conditions and then cultured on EMP coatings for 48 h. Integrin expression levels were assessed by flow cytometry analysis. It was found that attachment and spreading on EMP was inhibited by the synthetic RGD-containing peptide, but not by a synthetic RGE-peptide. Both PDL and gingival fibroblasts showed expression of the integrin subunits, alpha2, alpha5, beta1, and the integrin, alphavbeta3. Incubation with an antibody against the beta1 subunit significantly inhibited the attachment and spreading of PDL and gingival fibroblasts on EMP coatings. We conclude that integrins are involved in the interaction of PDL and gingival fibroblasts with EMP.

Adolescent↗
PubMedDate not supplied

Subcutaneous tissue fibroblasts transfected with muscle and nonmuscle actins: A good in vitro model to study fibroblastic cell plasticity.

Cultured fibroblasts develop several biochemical and morphological properties of smooth muscle cells, particularly the expression of alpha-smooth muscle actin, the actin isoform typical of vascular smooth muscle cells. They resemble modified fibroblasts or myofibroblasts observed in granulation tissue during wound repair and in fibrotic situations. We have analysed by immunolabeling the fate of exogenous epitope-tagged actin isoforms by transfection of the corresponding cDNAs into fibroblasts cultured from rat subcutaneous tissue. Tagged muscle actins were efficiently integrated into stress fibers and did not produce obvious changes in cell shape of transfected cells. Transfected nonmuscle actins in contrast changed the morphology and were not or poorly incorporated into stress fibers. These cultured subcutaneous fibroblasts behave similarly to smooth muscle cells when transfected with the same actin encoding cDNAs, indicating another common characteristic of these two cell types in sorting and targeting actin isoforms. Subcutaneous fibroblasts transfected with muscle and nonmuscle actin isoforms provide a good in vitro model to analyze the intracellular sorting of isoactins and to improve our knowledge of myofibroblast characterization and differentiation during tissue repair as well as to understand the relationships between modifications of actin cytoskeleton, adhesion and extracellular matrix proteins.

Actins↗
PubMed1975

Mitogenic effect of fibroblast growth factor on early passage cultures of human and murine fibroblasts.

Fibroblast growth factor (FGF), a polypeptide that has been shown to stimulate division in 3T3 cells, was tested for mitogenic effects on diploid, early-passage cells from human and murine sources. The quantitative assay of [3H]thymidine incorporation into acid-insoluble material showed that FGF at low concentrations (10 minus 9 M) was more effective than additional serum for provoking the initiation of DNA synthesis in human foreskin fibroblasts or mouse fibroblasts maintained in 5 or 10% serum, respectively. The growth of the human fibroblasts was twice as fast in the presence of FGF plus 10% calf serum as it was in the presence of 10% calf serum or 20% fetal calf serum alone. The addition of FGF to primary cultures of mouse fibroblasts in 0.4% serum resulted in a twofold increase in cell number compared to controls. In contrast to results obtained with 3T3 cells, neither insulin nor a glucocorticoid potentiated the effects of FGF on either human or mouse cells.

Animals↗
PubMed1981

Fibroblast stimulation in schistosomiasis. I. Stimulation in vitro of fibroblasts by soluble products of egg granulomas.

To gain further understanding of the pathogenesis of hepatic fibrosis in schistosomiasis, the interaction between egg granulomas and fibroblasts was investigated in an in vitro model. Egg granulomas isolated from livers of mice infected with Schistosoma mansoni or Schistosoma japonicum and cultured in vitro released a nondialyzable substance which stimulated proliferation in resting dermal fibroblasts. The release of the fibroblast-stimulating substance remained relatively constant during the first 48 hr of incubation with granulomas, during which time granulomas remained metabolically active in vitro. A dialyzable molecule(s) in granulomas supernatants interfered with fibroblast uptake of [3H]thymidine in vitro but did not inhibit cellular division. Granulomas supernatants also stimulated fibroblast secretion of prostaglandin E2 and caused an elevation in intracellular levels of cyclic adenosine monophosphate.

Animals↗
PubMed2004

Differential regulation by IL-1beta and EGF of expression of three different hyaluronan synthases in oral mucosal epithelial cells and fibroblasts and dermal fibroblasts: quantitative analysis using real-time RT-PCR.

Using "real-time RT-PCR", we assessed the expression of three different hyaluronan synthase genes, HAS1, HAS2, and HAS3, by measuring their mRNA amounts in cultured human oral mucosal epithelial (COME) cells, oral mucosal fibroblasts, and dermal fibroblasts, and investigated the effects of interleukin-1beta (IL-1beta) and epidermal growth factor (EGF). When COME cells were treated with IL-1beta or EGF, early and marked increases and subsequent rapid decreases were observed for all HAS genes and, moreover, actual changes in hyaluronan synthesis subsequently occurred. The effects of IL-1beta stimulation were concentration-dependent and the maximal response to the EGF stimulation was observed at a low concentration (0.1 ng per mL). When two different types of fibroblasts were treated with IL-1beta or EGF, increased expression with different degrees and rates of three different HAS genes and subsequent increased synthesis of hyaluronan were also observed. In addition, HAS1 gene expression was not detectable in the mucosal fibroblasts, while weak HAS3 gene expression was detected in the dermal fibroblasts. Taken together, it is likely that the regulation of the expression of the three different HAS genes is different between oral mucosa and skin, which may be of significance for elucidating some of the differences between these tissues in wound healing.

Cells, Cultured↗
PubMed1998

Increased activity of cathepsin B in fibroblasts isolated from primary melanoma in comparison to fibroblasts from normal skin.

We determined activity of cathepsin B in early-passage fibroblasts isolated from primary melanoma and in fibroblasts from normal skin. Our results show an up to 5-fold increase in activity of cathepsin B in the tumor-derived fibroblasts in comparison to the fibroblasts from normal skin. We conclude that fibroblasts isolated from melanoma tissue are altered with regard to their specific activity of cathepsin B and preserve this elevated activity in early-passage cell culture. The data support the idea that stromal cells are not passive elements of the peritumoral environment but actively participate in the production of proteolytic enzymes.

Cathepsin B↗
PubMed1997

Characterisation of fibroblast-like cells in pannus lesions of patients with rheumatoid arthritis sharing properties of fibroblasts and chondrocytes.

OBJECTIVE: To better understand the characteristics of synoviocytes located in the rheumatoid arthritis (RA) pannus. METHODS: One cell line, termed PSC, was cloned from RA pannus lesions. Phenotypic analysis was done by contrast microscopy, indirect immunostaining, and safranin O staining. Transcription of several protooncogenes and matrix degrading enzymes was evaluated. The expression of mRNA for collagen II was detected by in situ hybridisation. The ability of anchorage independent growth was assessed by soft agarose culture. RESULTS: PSCs showed a high transcription of protooncogenes c-fos, c-myc and c-jun. They also expressed mRNA for matrix degrading enzymes, such as collagenase, cathepsin B, and cathepsin L. Anchorage independent growth assay demonstrated that PSCs formed colonies in soft agar culture. Phenotypic analysis showed that this fibroblast-like PSC was stained intensely with anti-vimentin and anti-fibroblast antibody. In situ reverse transcriptase assay showed that the cell line expressed type II collagen mRNA. CONCLUSION: Alternative fibroblast-like cells were identified in the pannus lesion of RA sharing properties of fibroblasts and chondrocytes. These findings suggest that this fibroblast-like cell derived from pannus lesions may contribute to the destruction of the cartilage in RA.

Aged↗
PubMed1983

Complexity of control of tumorigenic expression in intraspecies hybrids of human SV40-transformed fibroblasts and normal human fibroblast cell lines.

Somatic cell hybrids between SV40-transformed human fibroblast cells and normal human fibroblasts were isolated and tested for growth in vitro and in athymic nu/nu (nude) mice. All hybrid cells formed by a cross of WI-18/VA-2, a tumorigenic SV40-transformed human fibroblast, with IMR-90 expressed T antigen and grew in the appropriate selective medium. However, tumorigenic potential ranged from completely suppressed to fully expressed in these hybrid cells. In addition, all hybrid cells formed between LNSV, a nontumorigenic SV40-transformed human fibroblast, and IMR-90 were nontumorigenic. Previous studies have shown that the tumorigenic potential of hybrids cells formed between a variety of human tumor cell lines and normal human fibroblasts is completely suppressed. These results imply that the genetic control of tumorigenic expression in virally transformed human cells differs from that seen in spontaneously arising human tumor cells.

Animals↗
PubMed2002

Protease-activated receptor-1-mediated DNA synthesis in cardiac fibroblast is via epidermal growth factor receptor transactivation: distinct PAR-1 signaling pathways in cardiac fibroblasts and cardiomyocytes.

Proteases elaborated by inflammatory cells in the heart would be expected to drive cardiac fibroblasts to proliferate, but protease-activated receptor (PAR) function in cardiac fibroblasts has never been considered. This study demonstrates that PAR-1 is the only known PAR family member functionally expressed by cardiac fibroblasts and that PAR-1 activation by thrombin leads to increased DNA synthesis in cardiac fibroblasts. The increase in DNA synthesis induced by PAR-1 substantially exceeds the effects of other G protein-coupled receptor agonists in this cell type. PAR-1 stimulates phosphoinositide hydrolysis and mobilizes intracellular calcium via pertussis toxin (PTX)-sensitive and PTX-insensitive pathways. Activation of PAR-1 leads to an increase in Src, Fyn, and epidermal growth factor receptor (EGFR) phosphorylation, with EGFR receptor transactivation by Src family kinases the major mechanism for PAR-1-dependent activation of extracellular signal-regulated kinase, p38-mitogen-activated protein kinase, and protein kinase B. Activation of PAR-1 also leads to an increase in DNA synthesis. PAR-1 signaling is highly contextual in nature, inasmuch as PAR-1 activates extracellular signal-regulated kinase and only weakly stimulates protein kinase B via a pathway that does not involve EGFR transactivation in cardiomyocytes. PAR-1 responses in cardiac fibroblasts and cardiomyocytes are predicted to contribute importantly to remodeling during cardiac injury and/or inflammation.

Animals↗
PubMed2006

Fibroblast foci are not discrete sites of lung injury or repair: the fibroblast reticulum.

BACKGROUND: Usual interstitial pneumonia (UIP), the pathologic correlate of idiopathic pulmonary fibrosis, contains characteristic discrete areas of fibroblasts, myofibroblasts, and newly formed collagen, termed "fibroblast foci." These lesions are argued to represent isolated sites of recurrent acute lung injury and suggested to be the mechanism of disease progression. We hypothesized that, rather than isolated, these lesions are part of an organized neoplasm. METHODS: Morphometric analysis of pentachrome-stained histologic sections of UIP was performed. Using point-counting technique on serial sections, fibroblast foci, arteries, and macrophage clusters were identified and we determined their individual "connectiveness" by estimating the Euler number. Two-dimensional micrographs were collated into a three-dimensional array from which a visual three-dimensional reconstruction could be constructed. Clonality analysis was performed using human androgen receptor gene methylation assay. RESULTS: Blood vessels show significant connectivity with a Euler number of 2, whereas macrophage clusters exhibited no connectivity. The fibroblast foci showed a high level of interconnection with Euler numbers ranging from 19 to 39. The computer generated three-dimensional models provide a visual confirmation of this connectiveness. Human androgen receptor gene methylation assay analysis of the foci showed balanced methylation consistent with polyclonality. CONCLUSIONS: The fibroblast foci of UIP are the leading edge of a complex reticulum that is highly interconnected and extends from the pleura into the underlying parenchyma. It is a reactive, rather than a malignant, process.

Disease Progression↗
PubMed1989

Hormonal regulation of hyaluronate synthesis in cultured human fibroblasts: evidence for differences between retroocular and dermal fibroblasts.

Fibroblasts derived from retroocular connective tissue and skin were propagated in culture in an effort to identify structural and functional differences in connective tissue which might explain the apparent region-specific involvement in Graves' disease. Striking morphological differences existed between cultured cells from the two anatomical sites. Inhibition of glycosaminoglycan (GAG) accumulation by T3 and dexamethasone in these cultures was compared. Confluent cultures were labeled with [3H]acetate, and total [3H]GAG was quantitated. Fibroblasts from the skin responded to T3 (100 nmol/L) and dexamethasone (100 nmol/L) with 27% and 55% inhibition of [3H]GAG accumulation, respectively (n = 12). In contrast, retroocular fibroblasts responded with 12% and 8% inhibition (n = 6) to the two hormones. When cultures from abdominal skin and retroocular tissue were treated with n-butyrate (10 mM), a compound known to inhibit hyaluronate specifically, they responded similarly with 78% and 83% inhibition, respectively. A pulse-chase study was performed using fibroblasts from both sites, and no [3H]GAG degradation could be detected for the duration of the chase period (up to 72 h). These results suggest that retroocular fibroblasts, likely participants in the pathogenesis of Graves' ophthalmopathy, do not respond vigorously to T3 or glucocorticoids in terms of inhibition of [3H]GAG synthesis as do their dermal counterparts.

Cells, Cultured↗
PubMed1996

Tenascin-X expression in tumor cells and fibroblasts: glucocorticoids as negative regulators in fibroblasts.

Tenascin-X has recently been shown to be a novel member of the tenascin family and its distribution is often reciprocal to that of tenascin-C in the developing mouse embryo. We have investigated the expression of tenascin-X in fibroblasts and carcinoma cells in culture. Tenascin-X protein was secreted in vitro in the conditioned media at an apparent molecular mass of approximately 450 kDa. In addition fibroblasts contained a major tenascin-X isoform of 220 kDa. On northern blots, a single major transcript with a size of approximately 13 kb was detected. No overexpression of tenascin-X protein was found in primary fibroblasts of the tenascin-C-gene knockout mice. Steroid hormone glucocorticoids, were found to downregulate tenascin-X mRNA levels and protein synthesis in fibroblasts but not carcinoma cells at physiological concentrations. None of the growth factors or cytokines examined affected the expression level of tenascin-X. As in vivo study, carcinoma cells were transplanted into nude mice. In contrast to the ubiquitous presence of tenascin-X in adult skin, expression of tenascin-X protein during tumorigenesis was found to be down-regulated considerably not only in tumor cells themselves but also in tumor stroma. These findings provide evidence that the expression of tenascin-X can be influenced by stromal-epithelial interactions. We have identified glucocorticoids as physiological inhibitors of tenascin-X and suggest that glucocorticoids may in part participate in the downregulation of tenascin-X in fibroblasts in vivo.

Animals↗
PubMed1976

Collagen resorption by fibroblasts. A theory of fibroblastic maintenance of the periodontal ligament.

Periodontal ligament fibroblasts contain numerous intracellular or cytosegragated collagen fibrils. These fibrils appear to be broken down within the lysosomal apparatus of the cells. There is an increase in this activity in fibroblasts associated with osteoclastic bone resorption. Cytoplasmic microfilaments and attachments to substrata indicate that the fibroblasts of the ligament have the potential of migration and cytoplasmic contraction. A theory of collagen fiber maintenance within the periodontal ligament is proposed which takes into account: (1) the motility and contractility of fibroblasts, (2) the phagocytic and degradative potential of fibroblasts, (3) the presence of intracellular collagen and (4) the reported high turnover rate of acid-insoluble collagen within the periodontium.

Actinomyces↗
PubMed2004

Inhibition of GM-CSF production in fibroblast-monocyte coculture by prednisone and effects of rhGM-CSF on human lung fibroblasts.

Fibroblasts play a sentinel role in asthmatic disease. They are the main constituents of connective tissue and are increased in number in the asthmatic lung. They are also capable of secreting a diverse repertoire of cytokines and are able to be activated by pro-inflammatory cytokines and cell-cell contact. Previously we have reported that normal human lung fibroblasts (NHLF) can be activated by monocytes (U937) through cell-cell contact to produce GM-CSF. Here we show that GM-CSF production from NHLF activated by monocyte contact is inhibited by prednisone, a synthetic glucocorticoid used in the treatment of asthma. GM-CSF is an acidic glycoprotein that potentiates development of cells in the granulocyte and macrophage lineage and is secreted at sites of peripheral inflammation. The receptor for GM-CSF was found on NHLF by flow cytometry and was able to be up-regulated by interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha and recombinant human (rh) GM-CSF. To test autocrine effects of GM-CSF on fibroblasts, rh GM-CSF was used in proliferation studies and was found to decrease fibroblast proliferation. Prednisone was used to block NF-kappaB activation and GM-CSF gene expression as well. These data indicate mechanism of action and treatment for cell-cell contact mediated inflammation of infiltrating monocytes with fibroblasts as seen in asthma and other diseases like graft versus host disease.

Anti-Inflammatory Agents↗
PubMed2000

Expression of molecular messages for angiogenesis by fibroblasts from aneurysmal abdominal aorta versus dermal fibroblasts.

BACKGROUND: The molecular messages which drive angiogenesis in the adventitia of an aneurysmal aorta are uncertain. The emergence of molecular phenotyping by cDNA expression arrays provides a simple and rapid method for a preliminary approach to the analysis of molecular messengers for neovascularization in cultured cells. In the present experiment, fibroblasts cultured from the aorta of a patient with abdominal aortic aneurysm (AAA) were compared with normal dermal fibroblasts, on an array that evaluates several mRNAs with known roles in angiogenesis. METHODS: RNA was isolated from fibroblasts and purified. Labelled cDNA probes were generated from a mixture of RNA and CDS primers. Atlas Array membranes (Clontech) were prehybridized by ExpressHyb buffer. The cDNA probes were then added to the membranes, which were exposed to Phospholmage Screen (Molecular Dynamics) and analysed by a dedicated computer program. RESULTS: The most significantly upregulated mRNAs in AAA (by comparison to dermal fibroblasts) were: MCAF, MDNCF, EGR-1, VEGF, FGF-7, Mal protein, Mac Marcks, Transducin, Interleukin-9 receptor, and TNF. CONCLUSION: VEGF and TNF were upregulated, as expected. However, the upregulation of monocyte chemotactic and activating factor (MCAF) and monocyte-derived neutrophil chemotactic factor (MDNCF) suggest that the fibroblast may be more significantly involved in driving the inflammatory response that leads to AAA than previously realized.

Aortic Aneurysm, Abdominal↗
PubMed2006

Differential effects of cortisol on MRC-5 fibroblasts and hypertrophic LL-29 fibroblasts.

Cortisol is a glucocorticoid secreted by the adrenal cortex that helps facilitate the body's response to stress and regulates the immune system. Glucocorticoid receptors can be found on most cell types and as a consequence, cortisol hormone plays an essential role on the body's physiologic systems. Cortisol has been shown to elicit differing responses from normal fibroblasts in comparison to hypertrophic fibroblasts. The purpose of this experiment was to analyze the differential effects of cortisol on normal MRC-5 fetal lung fibroblasts and hypertrophic LL-29 lung fibroblasts from a patient with idiopathic pulmonary fibrosis. The objectives of the experiment are to obtain and culture normal and hypertrophic lung fibroblasts, to challenge cells with subphysiological, physiological, and supraphysiological doses of cortisol (0.01 microg/dL, 0.2 microg/dL, 1 microg/dL) for 24, 48, and 72 hour incubation periods and to analyze cellular activity using the methods of cell count, protein assay, MDA, and morphological evaluation. Data collected from this study demonstrated variable response to cortisol by both cell lines. Striking results revealed that in LL-29 cells, supraphysiological dose of cortisol stimulated cell growth only in the 24-hour incubation period without showing any changes in number of micronucleoli or structural damage. In contrast, MRC-5 cells showed increased growth at a later stage (48 hours) with a dose specific increase with significantly increased micronucleoli numbers. In conclusion, the two cell lines differ in their response to cortisol concentration in a dose and time dependent manner. Cortisol concentrations did not induce structural damage throughout the experiment. These observations could help significantly in minimizing the traumatic side effects induced through stress conditions by employing intervention modalities to regulate systemic cortisol.

Cell Line↗