Bernard Coulomb
Research interests
-
InterestsCell Therapy, Fibroblast
Publications
-
2.78Impact points
Mechanisms of pathological scarring: role of myofibroblasts and current developments.
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society. 09/2011; 19 Suppl 1:s10-5.
Myofibroblasts play a key role in the wound-healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibrob... [more] Myofibroblasts play a key role in the wound-healing process, promoting wound closure and matrix deposition. These cells normally disappear from granulation tissue by apoptosis after wound closure, but under some circumstances, they persist and may contribute to pathological scar formation. Myofibroblast differentiation and apoptosis are both modulated by cytokines, mechanical stress, and, more generally, cell-cell and cell-matrix interactions. Tissue repair allows tissues and organs to recover, at least partially, functional properties that have been lost through trauma or disease. Embryonic skin wounds are repaired without scarring or fibrosis, whereas skin wound repair in adults always leads to scar formation, which may have functional or esthetic consequences, as in the case of hypertrophic scars, for example. Skin wound repair involves a precise remodeling process, particularly in the dermal compartment, during which fibroblasts/myofibroblasts play a central role. This article reviews the origins of myofibroblasts and their role in normal and pathological skin wound healing. This article focuses on traumatic skin wound healing, but largely, the same mechanisms apply in other physiological and pathological settings. Tissue healing in other organs is examined by comparison, as well as the stromal reaction associated with cancer. New approaches to wound/scar therapy are discussed.
-
1.87Impact points
Impact of photodynamic therapy on inflammatory cells during human chronic periodontitis.
Journal of photochemistry and photobiology. B, Biology. 12/2010; 101(3):348-54.
The aim of this study was to evaluate the effects of the photodynamic therapy (PDT) on the inflammatory infiltrate and on the collagen network organization in human advanced chronic periodontitis. Two different drug delivery systems (DDS) were tested (liposomes and nanoemulsions) to determine if the... [more] The aim of this study was to evaluate the effects of the photodynamic therapy (PDT) on the inflammatory infiltrate and on the collagen network organization in human advanced chronic periodontitis. Two different drug delivery systems (DDS) were tested (liposomes and nanoemulsions) to determine if the effects of PDT could differ according to the DDS used. Sixteen patients presenting two teeth with chronic advanced periodontitis and important tooth mobility with clinical indication of extraction were included in the group liposomes (group L, n=8) or in the group nanoemulsions (group N, n=8) in order to compare the effects of each DDS. Seven days before extractions one tooth of each patient was treated with PDT using phthalocyanine derivatives as photosensitizers and the contralateral tooth was taken as control. In group L the density of gingival collagen fibers (66±19%) was significantly increased (p<0.02) when compared to controls (35±21%). Concerning the antigen-presenting cells, PDT had differential effects depending on the drug delivery system; the number of macrophages was significantly decreased (p<0.05) in group L while the number of Langerhans cells was significantly decreased in group N (p<0.02). These findings demonstrate that PDT presents an impact on gingival inflammatory phenomenon during chronic periodontitis and leads to a specific decrease of antigen-presenting cells populations according to the drug delivery system used.
-
2.19Impact points
Phenotypic study of human gingival fibroblasts in a medium enriched with platelet lysate.
Journal of periodontology. 11/2010; 82(4):632-41.
The modulation abilities of gingival fibroblasts open new therapeutic strategies for the treatment of vascular diseases (e.g., aneurism) and irradiation burns. Culture media are classically supplemented with animal sera to provide nutriments. Unfortunately, because of their potential for interspecie... [more] The modulation abilities of gingival fibroblasts open new therapeutic strategies for the treatment of vascular diseases (e.g., aneurism) and irradiation burns. Culture media are classically supplemented with animal sera to provide nutriments. Unfortunately, because of their potential for interspecies transmission of microorganisms, these media are not used for cells destined for human transplantation. This preliminary phenotypic study aims to test a serum-free (SF) culture medium for human gingival fibroblasts (hGF) supplemented with human platelet lysates (PLs) for rapid cell expansion. An SF medium was first elaborated to compete with hGF proliferation in a reference medium containing 10% fetal bovine serum (BSmedium). Adhesion, proliferation, and doubling kinetics were run in the presence of PLs (SF+PL). Cytoskeletal proteins were analyzed and chromosomal abnormalities were evaluated by karyotype analyses. The SF+PL influence on secretion of molecules implied in tissue remodeling (i.e., matrix metalloproteinases [MMPs], their tissue inhibitors [TIMPs], and several growth factors) was studied. SF+PL increased the proliferation rate 1.5-fold in a week compared to BSmedium. Cytoskeleton protein expression was similar in BSmedium and in SF+PL. Chromosomal abnormalities were rare in SF+PL. MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, TIMP-1, and the growth factors interleukin-1β and -4 and transforming growth factor-β1 secretions were stable during the experiment. TIMP-2 and interleukin-6 were slightly decreased in SF+PL compared to BSmedium. While waiting confirmation from a proteomic approach, this SF culture medium could allow a secured faster hGF proliferation adapted for human cell transplant therapy.
-
4.64Impact points
Multipotent progenitor cells in gingival connective tissue.
Tissue engineering. Part A. 09/2010; 16(9):2891-9.
The gum has an exceptional capacity for healing. To examine the basis for this property and explore the potential of conferring it to organs with inferior healing capacity, we sought the presence of progenitor cells in gingival connective tissue. Colony-forming units of fibroblast-enriched cells fro... [more] The gum has an exceptional capacity for healing. To examine the basis for this property and explore the potential of conferring it to organs with inferior healing capacity, we sought the presence of progenitor cells in gingival connective tissue. Colony-forming units of fibroblast-enriched cells from gingival fibroblast cultures were assessed for expression of membrane markers of mesenchymal stem cells; capacity to differentiate into osteoblasts, chondroblasts, and adipocytes; and engraftment efficiency after in vivo transfer. On the basis of their ability to differentiate into several lineages, proliferate from single cells, induce calcium deposits, and secrete collagen in vivo after transfer on hydroxyapatite carriers, we suggest that this population represents gingival multipotent progenitor cells. The discovery of progenitor cells in gingival connective tissue may help improve our understanding of how the wounded gum is capable of almost perfect healing and opens the prospect of cellular therapy for wound healing using readily available cells at limited risk to the patient.
-
2.90Impact points
Fusiform Aneurysm Model in Rabbit Carotid Artery.
Journal of vascular research. 09/2009; 47(1):61-68.
Aims: To develop a reproducible and accessible model of elastase-induced fusiform aneurysm in carotid rabbit arteries. Methods: Elastase, at a concentration of 1-30 U, was incubated into the lumen of carotid rabbit arteries. Four weeks later, angiography, histomorphometry, immunohistochemistry and z... [more] Aims: To develop a reproducible and accessible model of elastase-induced fusiform aneurysm in carotid rabbit arteries. Methods: Elastase, at a concentration of 1-30 U, was incubated into the lumen of carotid rabbit arteries. Four weeks later, angiography, histomorphometry, immunohistochemistry and zymography were performed. Results: The optimal concentration of elastase in this model was 3 U according to the balance between mortality and thrombosis rates. Indeed, at 3 U, external carotid diameter increased from 1.9 +/- 0.1 to 3.1 +/- 0.4 mm (p < 0.0001) associated with degradation of elastic fibers, matrix metalloproteinase-9 secretion, apoptosis and macrophage infiltration. Conclusions: Our study underlines that abdominal aortic aneurysm can be reliably duplicated in an elastase-induced aneurysm in carotid artery, a much more accessible vessel.
-
4.97Impact points
Gingival fibroblast inhibits Mmp-7: Evaluation in an ex vivo aorta model.
Journal of molecular and cellular cardiology. 05/2009;
-
1.65Impact points
Increase of gingival matured dendritic cells number in elderly patients with chronic periodontitis.
Archives of oral biology. 10/2008;
OBJECTIVE: The purpose of this study was to evaluate the inflammatory cell subset proportions in the upper gingival connective tissue, including mature dendritic cells (DC) in elderly and younger patients with generalized chronic periodontitis in order to further understand the effect of aging on gi... [more] OBJECTIVE: The purpose of this study was to evaluate the inflammatory cell subset proportions in the upper gingival connective tissue, including mature dendritic cells (DC) in elderly and younger patients with generalized chronic periodontitis in order to further understand the effect of aging on gingival inflammatory phenomenon. METHODS: Gingival tissue specimens presenting chronic periodontitis from 8 elderly patients aged >75 (test group, group T) and from 8 younger patients aged 50-60 (considered as controls, group C) were analysed by immunohistochemistry using monoclonal antibodies against CD45RB, CD4, CD8, CD19, CD68, DC-SIGN, DC-LAMP molecules. The number of each immunolabelled cells subset was counted using image analysis. RESULTS: The difference in the number of CD45RB+leucocytes in the upper gingival connective tissue between groups was not significant permitting to use it as reference. As compared to group C, the lymphocyte subsets/CD45RB+leucocytes ratios tended to decrease in group T but the decrease was significant only for CD4+T lymphocytes/CD45RB+cells ratio (p<0.03). On the opposite, the ratios of antigen-presenting cells DC-SIGN+cells/CD45RB+cells and DC-LAMP+cells/CD45RB+cells were significantly increased (p<0.03 and <0.0001, respectively) in group T. Moreover, in group T the DC-LAMP+cells/DC-SIGN+cells ratio was significantly increased (p<0.05) showing an increased number of matured dendritic cells. CONCLUSION: During chronic periodontitis in elderly patients, our results show a decrease in the ratio of gingival CD4+lymphocyte subset associated with an increase in the ratios of antigen-presenting cells subsets and more particularly maturated DC-LAMP+dendritic cells.
-
From tadpole collagenase to human health care, the well-filled life of charles m. Lapiere, devoted to creativity, expertise, and kindness.
The international journal of lower extremity wounds. 04/2008; 7(1):49-50.
-
7.24Impact points
Preservation of rabbit aorta elastin from degradation by gingival fibroblasts in an ex vivo model.
Arteriosclerosis, thrombosis, and vascular biology. 10/2007; 27(9):1984-90.
OBJECTIVE: Embryo-like gingival healing properties are attributed to the gingival fibroblast (GF) and could be used as a model for other types of healing dysfunctions. Abdominal aortic aneurysm (AAA) formation is associated with elastin degradation and increase in matrix metalloproteinase (MMP)-9 ac... [more] OBJECTIVE: Embryo-like gingival healing properties are attributed to the gingival fibroblast (GF) and could be used as a model for other types of healing dysfunctions. Abdominal aortic aneurysm (AAA) formation is associated with elastin degradation and increase in matrix metalloproteinase (MMP)-9 activity. We aimed to validate the concept of using GF healing properties in arteries. METHODS AND RESULTS: We evaluated MMP-9 and its tissue inhibitor (TIMP-1) in rabbit aortic rings cultured in collagen gels with or without GFs and observed throughout 21 days. We also performed cocultures of human smooth muscle cells (hSMCs) with either gingival, dermal, or adventitial fibroblasts, and alone (control). In control arteries, elastic fibers became spontaneously sparse. In presence of GFs, elastic fibers were preserved. There was a dramatically reduced protein level of MMP-9 in coculture of aorta and GFs, in contrast with control aorta. MMP-9 expression was unaffected by GFs. MMP-9 inhibition was related to increased TIMP-1 secretion, TIMP-1 forming a complex with MMP-9. Cell cocultures of hSMC with GFs showed similar results. Dermal and adventitial fibroblasts did not affect MMP-9. CONCLUSIONS: Elastic fiber degradation was specifically preserved by GFs via reduction of MMP-9 protein level by increasing TIMP-1 synthesis. Vascular transfer of gingival fibroblasts could be a promising approach to treat AAA.
-
1.65Impact points
Do Langerhans cells behave similarly in elderly and younger patients with chronic periodontitis?
Archives of oral biology. 02/2007; 52(2):189-94.
OBJECTIVE: The purpose of this study was to compare the number, the distribution and the expression of markers of maturation of Langerhans cells (LC) in elderly and younger patients with chronic periodontitis in order to evidence the effect of aging on LC in inflammatory gingival tissue. METHODS: Gi... [more] OBJECTIVE: The purpose of this study was to compare the number, the distribution and the expression of markers of maturation of Langerhans cells (LC) in elderly and younger patients with chronic periodontitis in order to evidence the effect of aging on LC in inflammatory gingival tissue. METHODS: Gingival tissue specimens presenting chronic periodontitis from 8 elderly patients aged >75 (group E) and from 8 younger patients aged 50-60 (considered as controls, group C) were used for immunohistochemistry with monoclonal antibodies against CD45RB (leucocytes), CD1a (LC), markers of LC maturation (DC-LAMP, CD83) and number of immunolabelled cell subsets was evaluated using image analysis. RESULTS: The difference in the number of CD45RB+ leucocytes in the upper connective tissue between groups was not significant. In group E, the number of CD1a+ LC was significantly decreased (P<0.002) in the epithelium and significantly increased (P<0.0004) in the upper connective tissue. Furthermore, in group E, intraepithelial CD1a+ LC are more often observed in the upper epithelium and their dendritic processes were shorter and less numerous. Concerning the expression of markers of maturation, the numbers of intraepithelial DC-LAMP+ cells and CD83+ cells were significantly increased (P<0.0007 and P<0.02, respectively) in group E. CONCLUSION: During chronic periodontitis in elderly patients, the decrease in the number of intraepithelial LC and the alteration of dendritic processes could be balanced by a cellular distribution often observed in the upper epithelium associated with changes in cell maturation in response to bacterial elements.
-
1.55Impact points
Gingival fibroblasts inhibit MMP-1 and MMP-3 activities in an ex-vivo artery model.
Connective tissue research. 02/2007; 48(6):300-8.
The main arterial pathologies can be associated with a deregulation of remodeling involving matrix metalloproteinases (MMPs), whereas gingival healing is characterized by an absence of fibrosis or irreversible elastin/collagen degradation. The aim of our study was to evaluate the effect of gingival ... [more] The main arterial pathologies can be associated with a deregulation of remodeling involving matrix metalloproteinases (MMPs), whereas gingival healing is characterized by an absence of fibrosis or irreversible elastin/collagen degradation. The aim of our study was to evaluate the effect of gingival fibroblasts on MMP-1 and MMP-3 secretion in an organotypic artery culture. MMP-1 and MMP-3 secretions and activities (dot blots, zymography, ELISA) were evaluated in coculture of rabbit artery in the presence or not of gingival fibroblasts. MMP-1/TIMP-1 and MMP-3/TIMP-1 complexes forms were measured by ELISA. Complementary studies were performed using human aortic smooth muscle cells cocultured with adventitial, dermal, or gingival fibroblasts. Our results indicated that MMP-1 and MMP-3 free-forms activities were significantly reduced in coculture. This inhibition was linked to a significant increase of TIMP-1 leading to formation of TIMP-1/MMPs complexes. Due to the presence of gingival fibroblasts, the decrease in MMP-1 and MMP-3 efficiency thus contributes to diminish the degradation of artery. This cellular therapy strategy could be promising in artery pathologies treatment.
-
7.88Impact points
Dense fibrillar collagen matrices: a model to study myofibroblast behaviour during wound healing.
Biomaterials. 10/2006; 27(25):4443-52.
Fibroblastic cells play an important part in wound healing. Human dermal fibroblasts seeded onto three-dimensional fibrillar collagen matrices migrate into the collagen network and differentiate into myofibroblasts. In order to evaluate the use of collagen matrices as model systems for studying myof... [more] Fibroblastic cells play an important part in wound healing. Human dermal fibroblasts seeded onto three-dimensional fibrillar collagen matrices migrate into the collagen network and differentiate into myofibroblasts. In order to evaluate the use of collagen matrices as model systems for studying myofibroblast phenotype during wound healing, myofibroblast behaviour migrating into dense or loose matrices was compared. The effect of collagen concentration on cell morphology, remodelling, proliferation and apoptosis of human myofibroblasts was evaluated. Myofibroblasts within dense collagen matrices (40 mg/ml) were spindle shaped, similar to cells observed during tissue repair. In contrast, cells within loose matrices (5mg/ml) were more rounded. Matrix hydrolysis activities (MT1-MMP and MMP2) did not differ between the two collagen concentrations. The myofibroblast proliferation rate was measured after 24h bromodeoxyuridine incorporation (BrdU). Cells in dense collagen matrices proliferated at a higher rate than cells in loose matrices at each culture time point tested. For example, 40% of cells in dense matrices were replicating compared to 10% of cells in loose matrices after 28 days in culture. Apoptotic cells were only detected in dense matrices from day 21 onwards when cells had already migrated into the collagen network. Taken together, these results show that a high collagen concentration has a stimulatory effect on myofibroblast proliferation and apoptosis, two important events in wound healing. Thus, dense matrices can be used to create controlled conditions to study myofibroblast phenotype.
-
3.24Impact points
Infrared radiation induces the p53 signaling pathway: role in infrared prevention of ultraviolet B toxicity.
Experimental dermatology. 03/2006; 15(2):130-7.
We have previously observed that preirradiation with naturally occurring doses of near-infrared (IR) protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. This effect was observed in temperature-controlled conditions, without heat shock protein (Hsp72-70) induction. M... [more] We have previously observed that preirradiation with naturally occurring doses of near-infrared (IR) protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. This effect was observed in temperature-controlled conditions, without heat shock protein (Hsp72-70) induction. Moreover, IR inhibited UVB-induced apoptosis by modulating the Bcl2/Bax balance, pointing to a role of p53. Here, we show for the first time that p53-deficient SaOs cells are not protected from UVB cytotoxicity by IR preirradiation, suggesting that the response to IR is p53-dependent. Thus, we investigated the effect of IR on the p53 signaling pathway. Normal human dermal fibroblasts exposed in vitro to IR accumulated p53 protein, involving p53 stabilization and phosphorylation of serine 15 (Ser15) and Ser20. IR-induced p53 accumulation correlated with increased expression of p21 and GADD45, showing that IR also stimulates p53 transcriptional activity. By modulating UVB-induced targets of the p53 signaling pathway, IR irradiation appears to anticipate the UVB response and to prepare cells to better resist subsequent UV-induced stress. This is reinforced by the fact that IR preirradiation reduces the formation of UVB-induced thymine dimers.
-
2.51Impact points
Dextran derivatives modulate collagen matrix organization in dermal equivalent.
Journal of biomaterials science. Polymer edition. 02/2006; 17(5):499-517.
Dextran derivatives can protect heparin binding growth factor implied in wound healing, such as transforming growth factor-beta1 (TGF-beta1) and fibroblast growth factor-2 (FGF-2). The first aim of this study was to investigate the effect of these compounds on human dermal fibroblasts in culture wit... [more] Dextran derivatives can protect heparin binding growth factor implied in wound healing, such as transforming growth factor-beta1 (TGF-beta1) and fibroblast growth factor-2 (FGF-2). The first aim of this study was to investigate the effect of these compounds on human dermal fibroblasts in culture with or without TGF-beta1. Several dextran derivatives obtained by substitution of methylcarboxylate (MC), benzylamide (B) and sulphate (Su) groups were used to determine the effects of each compound on fibroblast growth in vitro. The data indicate that sulphate groups are essential to act on the fibroblast proliferation. The dextran derivative LS21 DMCBSu has been chosen to investigate its effect on dermal wound healing process. Fibroblasts cultured in collagenous matrices named dermal equivalent were treated with the bioactive polymer alone or associated to TGF-beta1 or FGF-2. Cross-sections of dermal equivalent observed by histology or immunohistochemistry, demonstrated that the bioactive polymer accelerates the collagen matrices organization and stimulates the human type-III collagen expression. This bioactive polymer induces apoptosis of myofibroblast, property which may be beneficial in treatment of hypertrophic scar. Culture media analyzed by zymography and Western blot showed that this polymer significantly increases the secretion of zymogen and active form of matrix metalloproteinase-2 (MMP-2), involved in granulation tissue formation. These data suggest that this bioactive polymer has properties which may be beneficial in the treatment of wound healing.
-
7.88Impact points
Fibroblast populated dense collagen matrices: cell migration, cell density and metalloproteinases expression.
Biomaterials. 06/2005; 26(13):1533-43.
Dense collagen matrices obtained by using the property of type I collagen to form liquid crystals at high concentrations, were shown to be colonized by human dermal fibroblasts (Biomaterials 23 (2002) 27). In order to evaluate them as possible tissue substitutes, we investigated in this study the me... [more] Dense collagen matrices obtained by using the property of type I collagen to form liquid crystals at high concentrations, were shown to be colonized by human dermal fibroblasts (Biomaterials 23 (2002) 27). In order to evaluate them as possible tissue substitutes, we investigated in this study the mechanism of cell colonization. Fibroblasts were seeded at the surface of collagen matrices at concentrations of 5 and 40 b mg/ml. Cell density and migration were estimated from histological sections over 28 days within 500 microm thick matrices. At day 14, migration started in the 40 mg/ml matrices, attaining 320 microm in distance and 5500 cell/mm(3) in density at day 28. As zymography and western blot techniques demonstrated production of collagenase 1 (MMP1) and gelatinase A (MMP2) in culture medium, collagen hydrolysis was required for cells to penetrate the collagen network. Furthermore, the presence of MMP1 and MMP2 and their tissue inhibitors TIMP1 and TIMP2 was revealed by immunohistochemistry. We presently show that 40 mg/ml collagen matrices are colonized by human dermal fibroblasts and reach, at day 28, a density close to that measured in human dermis.
-
5.54Impact points
Infrared radiation affects the mitochondrial pathway of apoptosis in human fibroblasts.
The Journal of investigative dermatology. 12/2004; 123(5):823-31.
We have previously observed that near-infrared (IR) pre-irradiation protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. Here, we show that IR pre-irradiation of human fibroblasts inhibited UVB activation of caspase-9 and -3, leading us to study early events in the m... [more] We have previously observed that near-infrared (IR) pre-irradiation protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. Here, we show that IR pre-irradiation of human fibroblasts inhibited UVB activation of caspase-9 and -3, leading us to study early events in the mitochondrial apoptotic pathway after IR irradiation. IR irradiation led to a partial release of cytochrome c and Smac/Diablo but not apoptosis-inducing factor (AIF). This was accompanied by a slight but transient decrease in the mitochondrial membrane potential (Deltapsim) and by the insertion of Bax into mitochondrial membrane. Early apoptotic events in the mitochondrial pathway thus occurred after IR irradiation despite a lack of caspase-9 and -3 activation. This could be explained by the induction by IR of the expression of heat shock protein Hsp27, which is known to prevent apoptosome assembly. Furthermore, the balance between pro-apoptotic (i.e., Bax) and anti-apoptotic (i.e., Bcl-2 or Bcl-xL) proteins, which was rather pro-apoptotic after IR exposure, became anti-apoptotic 24 h later, suggesting a protective effect. Together, these actions could also contribute to prepare the cell to resist UVB-triggered apoptosis. Finally, isolated rat liver mitochondria-released cytochrome c in response to IR, demonstrating that mitochondria were a primary target of IR radiation.
-
3.24Impact points
ERK activation by mechanical strain is regulated by the small G proteins rac-1 and rhoA.
Experimental dermatology. 03/2004; 13(2):70-7.
Physical forces play an important role in regulating cell functions. We applied mechanical strain to human fibroblasts by magnetic attraction of superparamagnetic arginine-glycine-aspartic acid (RGD)-coated beads. We confirmed that the MAP kinases Erk and p38 are activated by mechanical strain, and ... [more] Physical forces play an important role in regulating cell functions. We applied mechanical strain to human fibroblasts by magnetic attraction of superparamagnetic arginine-glycine-aspartic acid (RGD)-coated beads. We confirmed that the MAP kinases Erk and p38 are activated by mechanical strain, and went further by demonstrating the activation of Elk-1 by mechanical strain, mainly through a MEK-Erk pathway. Transfection of a dominant negative form of the G protein rac-1 (rac T17N), and inhibition of PI3K, an effector of rac-1, efficiently prevented Elk-1 activation by mechanical forces. Transfection with C3 transferase, known to inhibit rhoA, and inhibition of rock (a downstream effector of rhoA), gave similar results. However, contrary to the active form of rhoA (rho G14V), transfection of the active form of rac-1 (rac G12V) induced Elk activation and mimicked the effects of mechanical strain. These results point out that the two small G proteins rhoA and rac-1 participate in cell sensitivity to mechanical strain and lead to the modulation of the Erk pathway.
-
2.51Impact points
Effect of a dextran derivative associated with TGF-beta1 or FGF-2 on dermal fibroblast behaviour in dermal equivalents.
Journal of biomaterials science. Polymer edition. 02/2004; 15(11):1463-80.
Dextran derivatives that mimic the action of heparin have been shown to protect heparin-binding growth factors, such as Transforming Growth Factor-beta1 (TGF-beta1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a dextran derivative which ... [more] Dextran derivatives that mimic the action of heparin have been shown to protect heparin-binding growth factors, such as Transforming Growth Factor-beta1 (TGF-beta1) and Fibroblast Growth Factor-2 (FGF-2). The aim of this study was to investigate the effect of LS21 DMCBSu, a dextran derivative which contains methylcarboxylate, benzylamide and sulfate groups, both by itself and when combined with TGF-beta1 and FGF-2, on the behaviour of fibroblasts. Two systems were assessed: a monolayer culture and three-dimensional collagenous matrices (dermal equivalent). Polymeric biomaterial LS21 DMCBSu and LS21 DMCBSu associated with either TGF-beta1 or FGF-2, were added to the monolayer culture on day 3. After 7 days of culture the number of cells was determined. Two treatments were carried out on the dermal equivalents: 9 days of treatment from day 0 to day 9 of culture and 9 days of treatment from day 21 to day 30 of culture for the premature and the mature dermal equivalents respectively. In the monolayer culture, the bioactive polymer produced a slight increase in fibroblast growth (10% with 10 microg/ml of LS21 DMCBSu) and promoted the stimulating effect of the growth factors on cell growth. In the premature dermal equivalents growth was stimulated by 20% when 10 microg/ml LS21 DMCBSu was added. The dextran derivative mixed with TGF-beta1 slightly inhibited the growth effect of the growth factor in the dermal equivalents. The functionalized dextran with FGF-2 enhanced the stimulating effect of the growth factor in the premature dermal equivalent. A significant increase in cell growth was observed with the fibroblasts treated with the FGF-2 LS21 DMCBSu mixture and FGF-2 (51% and 40%, respectively). However, none of the described treatments affected the cell growth in the mature dermal equivalent. Furthermore, the dextran derivative had no effect on dermal contraction under these experimental conditions (3D culture).
-
2.25Impact points
p38 mitogen-activated protein kinase activation by ultraviolet A radiation in human dermal fibroblasts.
Photochemistry and photobiology. 09/2003; 78(2):168-74.
UVA radiation penetrates deeply into the skin reaching both the epidermis and the dermis. We thus investigated the effects of naturally occurring doses of UVA radiation on mitogen-activated protein kinase (MAPK) activities in human dermal fibroblasts. We demonstrated that UVA selectively activates p... [more] UVA radiation penetrates deeply into the skin reaching both the epidermis and the dermis. We thus investigated the effects of naturally occurring doses of UVA radiation on mitogen-activated protein kinase (MAPK) activities in human dermal fibroblasts. We demonstrated that UVA selectively activates p38 MAPK with no effect on extracellular-regulated kinases (ERK1-ERK2) or JNK-SAPK (cJun NH2-terminal kinase-stress-activated protein kinase) activities. We then investigated the signaling pathway used by UVA to activate p38 MAPK. L-Histidine and sodium azide had an inhibitory effect on UVA activation of p38 MAPK, pointing to a role of singlet oxygen in transduction of the UVA effect. Afterward, using prolonged cell treatments with growth factors to desensitize their signaling pathways or suramin to block growth factor receptors, we demonstrated that UVA signaling pathways shared elements with growth factor signaling pathways. In addition, using emetine (a translation inhibitor altering ribosome functioning) we detected the involvement of ribotoxic stress in p38 MAPK activation by UVA. Our observations suggest that p38 activation by UVA in dermal fibroblasts involves singlet oxygen-dependent activation of ligand-receptor signaling pathways or ribotoxic stress mechanism (or both). Despite the activation of these two distinct signaling mechanisms, the selective activation of p38 MAPK suggests a critical role of this kinase in the effects of UVA radiation.
-
Cutaneous wound healing: myofibroblastic differentiation and in vitro models.
The international journal of lower extremity wounds. 07/2003; 2(2):60-8.
Wound healing is an interactive, dynamic 3-phased process. During the formation of granulation tissue, many fibroblastic cells acquire some morphological and biochemical smooth muscle features and are called myofibroblasts. Myofibroblasts participate in both granulation tissue formation and remodeli... [more] Wound healing is an interactive, dynamic 3-phased process. During the formation of granulation tissue, many fibroblastic cells acquire some morphological and biochemical smooth muscle features and are called myofibroblasts. Myofibroblasts participate in both granulation tissue formation and remodeling phases. Excessive scarring, which is a feature of impaired healing, is a serious health problem that may affect the patient's quality of life. The treatment costs of such lesions are high, and often, the results are unsatisfactory. To understand the wound healing process better and to promote improvement in human healing, models are needed that can predict the in vivo situation in humans. In vitro models allow the study of cell behavior in a controlled environment. Such modeling partitions and reduces to small scales behavior perceived in vivo. This article is focused on "fibroblasts". In vitro models to study wound healing, the role of (myo)fibroblasts, and skin reconstruction in tissue replacement and promotion of wound healing are discussed.
Following (5)
-
Laetitia Frank
Hyphen Biomed company -
Antonio Cláudio Tedesco
Universidade de São Paulo -
Louis Dubertret
Fondation René Touraine -
Karim Senni
Université René Descartes - Paris 5 -
Vincent Sarrazy
University of Toronto
