SEARCH · PubMed Health

Results for “FIBROBLASTS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,585 records · Page 88Linked to original sources

PubMed2002

Triamcinolone stimulates bFGF production and inhibits TGF-beta1 production by human dermal fibroblasts.

BACKGROUND: Triamcinolone acetonide has been shown to decrease both cellular proliferation and collagen production by dermal fibroblasts. An alteration of cytokine levels may mediate these effects. OBJECTIVE: To delineate the effect of triamcinolone acetonide on both cellular proliferation and the production of basic fibroblast growth factor (bFGF) and transforming growth factor beta1 (TGF-beta1) by human fibroblasts grown in a serum-free in vitro model. METHODS: Human normal and keloid dermal fibroblasts were propagated in a serum-free in vitro model with exposure to 0, 5, 10, or 20 microm triamcinolone acetonide for 0, 24, 72, or 96 hours. Cell counts were determined by phase contrast microscopy. Levels of bFGF and TGF-beta1 in the supernatants were determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: In our study, 20 microm triamcinolone acetonide caused statistically significant increases in the peak levels of bFGF for normal and keloid fibroblast cell lines (P < 0.05). It also caused statistically significant decreases in the level of TGF-beta1 for normal and keloid fibroblast cell lines. For the keloid fibroblasts, 10 microm triamcinolone acetonide also caused a statistically significant decrease in the level of TGF-beta1. CONCLUSION: We conclude from these results that triamcinolone acetonide increases the production of bFGF and decreases production of TGF-beta1 by human dermal fibroblasts.

Analysis of Variance↗

PubMedDate not supplied

In vitro fibroblast populated collagen lattices are not good models of in vivo clinical wound healing.

In chronic wounds, the healing process is prolonged and incomplete, proceeding in an uncoordinated manner, and resulting in poor anatomical and functional outcome. There have been numerous attempts to discover models that mimic human wound healing processes. The fibroblast populated collagen lattice is one such model that has been proposed. This study evaluated whether the fibroblast populated collagen lattice can be a model of chronic wound healing using the pressure ulcer as a paradigm. Fibroblast cultures of wound biopsies and wound volume measurements were obtained serially during a four arm blinded, placebo-controlled sequential cytokine clinical trial of pressure ulcers. Fibroblasts obtained from study patients were added to collagen lattices and contraction was determined daily for 10 days. Collagen gel-area measurements were converted to reflect percentage of gel contraction. These data of both edge and base wound biopsies on days 0, 10, and 36 were categorized into treatment groups and one-way analysis of variance showed no significant differences in contraction among these groups. When considering all fibroblast populated collagen lattices, there was significantly greater contraction at days 10 and 36 for cells from both edge and base biopsies compared to day 0 (p < 0.05). The Spearman Rank Correlation test comparing all patients with fibroblast populated collagen lattice results from fibroblasts obtained at the edge or base of the wound at days 0, 10, and 36 and clinical pressure ulcer healing on day 36 showed no correlation. This lack of correlation not only persisted for each of the four treatment arms but also for responder status based on decrease in wound volume over the 35 day trial period. In conclusion, chronic wound healing is a complex process that is not modeled by in vitro fibroblast populated collagen lattices.

Collagen↗

PubMed1982

Replication and phenotypic expression of control and scleroderma human fibroblasts: responses to growth factors.

To explore the mechanism of increased collagen synthesis by scleroderma skin fibroblasts in vitro, control and scleroderma fibroblasts were compared in confluent monolayer cultures growth-arrested by serum deprivation; responses to optimal mitogenic doses of platelet-derived growth factor, fibroblast growth factor, epidermal growth factor and nerve growth factor were compared. Platelet-derived growth factor had a selective mitogenic effect on control skin fibroblasts not observed with scleroderma skin fibroblasts. None of the factors studied had a selective effect on collagen synthesis independent of cell replication; scleroderma and control fibroblasts responded similarly. Therefore, the growth factors studied may not be involved in generating the activated scleroderma fibroblast directly; platelet-derived growth factor may play an indirect role in fibroblast replication in human fibrotic disorders.U

Cell Division↗

PubMed1989

Acidic fibroblast growth factor mRNA is expressed by cardiac myocytes in culture and the protein is localized to the extracellular matrix.

Acidic and basic fibroblast growth factors are heparin-binding proteins that induce cellular proliferation, mesodermal development, and vascular growth. As such, they may be important in cardiac development and disease. To determine whether cardiac myocytes contain fibroblast growth factors, neonatal rat cardiac myocytes were studied in primary culture and compared to primary cultures of nonmyocyte cardiac cells. Northern blot analysis revealed a 4.0-kilobase mRNA in myocytes that hybridized to acidic fibroblast growth factor cDNA and was not detectable in nonmyocyte cultures. Western blot analysis demonstrated the accumulation of a 15-kDa peptide with immunological identity to acidic fibroblast growth factor in extracts of extracellular matrix from myocyte cultures that was not detectable in similar extracts of nonmyocyte extracellular matrix. No acidic fibroblast growth factor-like protein was detectable in cellular lysates from either myocyte or nonmyocyte cultures. These results demonstrate that neonatal cardiac myocytes express acidic fibroblast growth factor mRNA and deposit a protein with immunological identity to acidic fibroblast growth factor into the extracellular matrix. The results suggest that acidic fibroblast growth factor produced by cardiac myocytes may mediate, through both paracrine and autocrine mechanisms, such diverse processes as myocyte differentiation, cellular proliferation, and vascular growth in the heart.

Animals↗

PubMed1987

Production of a growth factor(s) by fibroblasts from the lungs of ventilated premature baboons and oxygen-exposed adult hamsters.

Among the pathologic findings in infants succumbing to bronchopulmonary dysplasia are peribronchiolar and alveolar fibrosis. We examined the possibility that endogenously produced growth factors might contribute to these fibrotic changes through stimulation of fibroblast replication, with a resulting increase in collagen synthesis. We cultured fibroblasts from the lungs of prematurely delivered baboons and adult hamsters exposed to 100% oxygen and tested the media from these cells to see if they produced a factor(s) that was mitogenic to normal fibroblasts. We found that lung fibroblasts from baboons delivered prematurely at 140 days of gestation and ventilated for 6 days with 100% oxygen produced a factor(s) that supported fibroblast growth. A similar factor was also secreted by fibroblasts from normal term newborn baboon lungs and from the lungs of adult hamsters exposed to 100% oxygen for 4 to 8 days. Growth factor was not secreted by lung fibroblasts from 140-day non-breathing or 24-h-ventilated premature baboons, adult baboons, or hamsters not exposed oxygen. The growth-promoting substance is apparently a progression factor that is heat labile and inactivated by exposure to trypsin. These findings indicate that exposure of both the premature and adult lung to high concentrations of oxygen causes the elaboration of a growth factor that may induce fibroblast hyperplasia. This action may result in an increased production of connective tissue proteins and thereby contribute to the development of the fibrosis seen in bronchopulmonary dysplasia.

Animals↗

PubMed1982

Fibroblasts from a patient with leprechaunism are resistant to insulin, epidermal growth factor, and somatomedin C.

Leprechaunism is a rare inherited disorder characterized by severe intrauterine growth retardation and insulin resistance. Cultured skin fibroblasts from an infant with Leprechaunism were previously reported to show decreased stimulation of DNA synthesis by insulin despite apparently normal binding of [125I]insulin and [125I]somatomedin C. We have now further investigated the growth of this patient's fibroblasts and compared their metabolic responses to insulin and various peptide growth factors with responses in normal foreskin-derived fibroblasts. The doubling time of Leprechaun fibroblasts was prolonged (90 vs. 29 h), and their morphology was abnormal. Stimulation of [3H]glucose uptake was minimal with low insulin levels (1--10 ng/ml) relative to controls, but was comparable at higher insulin concentrations (1--10 micrograms/ml). Stimulation of [3H] aminoisobutyric acid uptake by insulin, epidermal growth factor (EGF), multiplication-stimulating activity, and somatomedin C (Sm-C) in Leprechaun cells was diminished relative to control cells at all concentrations tested. Furthermore, stimulation of [3H]thymidine incorporation in Leprechaum cells by EGF, Sm-C, and fibroblast growth factor was also subnormal. Binding of [125I]EGF to Leprechaun fibroblasts was not decreased. It is concluded that fibroblasts from this patient are resistant to the metabolic effects of insulin, EGF, Sm-C, and fibroblast growth factor. Since receptors for three of these peptides are apparently normal, it is likely that the defect in these cells is at the postreceptor level, perhaps involving a metabolic pathway common to the action of multiple growth factors.

Aminoisobutyric Acids↗

PubMed1998

A role for the fibroblast growth factor receptor in cell fate decisions in the developing vertebrate retina.

The mature vertebrate retina contains seven major cell types that develop from an apparently homogenous population of precursor cells. Clonal analyses have suggested that environmental influences play a major role in specifying retinal cell identity. Fibroblast growth factor-2 is present in the developing retina and regulates the survival, proliferation and differentiation of developing retinal cells in culture. Here we have tested whether fibroblast growth factor receptor signaling biases retinal cell fate decisions in vivo. Fibroblast growth factor receptors were inhibited in retinal precursors in Xenopus embryos by expressing a dominant negative form of the receptor, XFD. Dorsal animal blastomeres that give rise to the retina were injected with cDNA expression constructs for XFD and a control non-functional mutant receptor, D48, and the cell fates of transgene-expressing cells in the mature retina determined. Fibroblast growth factor receptor blockade results in almost a 50% loss of photoreceptors and amacrine cells, and a concurrent 3.5-fold increase in Müller glia, suggesting a shift towards a Müller cell fate in the absence of a fibroblast growth factor receptor signal. Inhibition of non-fibroblast-growth-factor-mediated receptor signaling with a third mutant receptor, HAVO, alters cell fate in an opposite manner. These results suggest that it is the balance of fibroblast growth factor and non-fibroblast growth factor ligand signals that influences retinal cell genesis.

Animals↗

PubMed2001

Silica and its antagonistic effects on transforming growth factor-beta in lung fibroblast extracellular matrix production.

BACKGROUND: Silicosis, a pneumoconiosis marked by interstitial pulmonary fibrosis, is caused by inhalation of free crystalline silica particles. When silica particles are injected into the lower lung, they are translocated across the epithelium into the interstitial space, where macrophage-derived growth factors affect lung fibroblast proliferation and collagen deposition. We hypothesized that silica may act directly on pulmonary fibroblasts modifying extracellular matrix (ECM) synthesis and that the effects of silica may be mediated by transforming growth factor-beta (TGFbeta) overproduction. METHODS: To test this hypothesis, we studied a human lung fibroblast cell line (WI-1003) exposed to silica in vitro. We investigated cell morphology by electron microscopic procedure, cell growth, collagen production, and glycosaminoglycans (GAG) composition by radiolabeled precursors. Cytokine and growth factor synthesis were evaluated by specific enzyme-linked immunoadsorbent assay kits and Northern blotting analysis. RESULTS: Pulmonary fibroblasts internalized silica particles without detectable cell damage. Silica directly stimulated collagen synthesis and decreased the amount of 3H-glucosamine-labeled GAG. Silica-treated fibroblasts secreted less TGFbeta than untreated controls, antagonized the stimulatory effect of TGFbeta on ECM synthesis, and reversed TGFbeta-induced inhibition of cell proliferation. Northern blotting analysis showed increased interleukin-1alpha (IL-1alpha) mRNA after silica treatment. IL-1alpha had no influence on collagen synthesis but increased the number of WI-1003 fibroblasts. CONCLUSIONS: These results support our hypothesis that lung fibroblasts are direct silica targets. However, contradicting our hypothesis, silica antagonized TGFbeta activities through a TGFbeta downregulation and an IL-1alpha upregulation. The complex pattern of TGFbeta and IL-1alpha regulation in pulmonary fibroblasts is imbalanced by silica exposure and might play a key role in silica-mediated pulmonary fibrosis.

Cell Division↗

PubMed1997

Protection of rat myocardium by mitogenic and non-mitogenic fibroblast growth factor during post-ischemic reperfusion.

The effects of acidic fibroblast growth factor (FGF-1) and basic fibroblast growth factor (FGF-2) and a non mitogenic form of FGF1 on myocardial ischemia and reperfusion were assessed. Rats underwent 10 minutes of coronary artery occlusion followed by 24 hours of reperfusion. Creatinine kinase content of the affected myocardium showed that both fibroblast growth factors 1 and 2 effectively protected against ischemia reperfusion injury (p < 0.01), and that the vasoactive but nonmitogenic form of the FGF1 was equally protective (p < 0.01 versus control + vehicle). The results were confirmed by light and electron-microscopy histological studies. Histological evaluations after treatment with the non-mitogenic fibroblast growth factor 1 showed that it did not generate the severe hyperplasia and connective tissue disorganization observed with the native mitogenic proteins. The possibility of using a non-mitogenic form of fibroblast growth factor for cardio-protection circumvents many of the potentially undesirable effects that may derive from systemically introducing broad spectrum acting fibroblast growth factors in vivo. This myocardial protection observed 24 hours after the treatment with fibroblast growth factors, and the efficacy of the non-mitogenic form of the protein, also suggest that the protective effect of fibroblast growth factors may be due to the increased blood flow rather than to angiogenesis.

Animals↗

PubMed2000

Fibronectin/fibroblast growth factor/cell matrix signaling pathways and reciprocal membrane interaction may be the regulators of cell growth and apoptosis in Trypanosoma musculi in co-cultures with fibroblasts.

Trypanosoma musculi cultivated in medium containing serum alone or in the absence of fibroblasts in vitro were transformed into rounded, immotile cells, incapable of division and infectivity. Only in close contact with fibroblasts could the parasites survive and grow indefinitely. This report established the identity of the splenic 'sustentacular' cells as fibroblasts and utilized immunocytochemistry to demonstrate the putative cytoskeletal and membrane-associated molecules that may be involved in the control of growth and division, and apoptosis of T. musculi in vitro. The results indicated that cells that reacted intensely for fibroblast growth factor (FGF) also displayed a complex cytoskeletal system of F-actin bands underlying the plasma membrane of the fibroblast cell body and its numerous processes. Among the cytoskeletal and membrane glycoproteins, fibronectin, I-CAM, laminin, occludin, vinculin and desmin were most prominent. Fibronectin was most highly enhanced on the cell membrane and deposited as 'finger prints or tracks' on the extracellular culture surfaces. Transmission and scanning electron microscopy confirmed the intimate contact between trypanosomes and fibroblasts, however, neither membrane fusion or junctions were apparent. Our results suggested that a fibroblast-derived, membrane-associated factor appeared to be the putative growth regulator and apoptosis inhibitor in co-cultures of spleen-derived fibroblasts and T. musculi.

Animals↗

PubMed2001

[The stimulating effects of bFGF on fibroblast function and its C-fos gene expression].

OBJECTIVE: To study the stimulating effects of basic fibroblast growth factor(bFGF) on fibroblast function and its ability to expression of c-fos gene. Furthermore, to explore the possible network action between bFGF and oncogene in modulating wound healing. METHODS: Cultured rat fibroblasts were divided into bFGF stimulating group and control group. Fibroblasts in bFGF stimulating group were treated with bFGF in a dosage of 40 ng/culture hole, while the control fibroblasts were treated with the same vehicle without bFGF. The morphology, cell vitality and their ability to express c-fos gene in the fibroblasts in both groups were studied with MTT and immunohistochemical methods. RESULTS: All fibroblasts in bFGF treated groups were enlarged and showed increased vitality with MTT method. C-fos gene expression in bFGF stimulating group was increased, especially in nucleus when compared with those in control group. CONCLUSION: The results show that the function and the ability to express c-fos gene in bFGF treated fibroblasts are enhanced. Combined with our previous studies, it may make a conclusion that there is a network regulation mechanism between growth factors and some oncogenes.

Animals↗

PubMed1986

The cellular mechanism of glucocorticoid acceleration of fetal lung maturation. Fibroblast-pneumonocyte factor stimulates choline-phosphate cytidylyltransferase activity.

The cellular mechanism by which glucocorticoids stimulate phosphatidylcholine biosynthesis has been studied in the fetal rat lung in vivo and in cultured fetal rat lung cells of varying levels of complexity. Administration of dexamethasone to pregnant rats at 18 days gestation resulted in a significant increase in saturated phosphatidylcholine content in fetal lung 24 h after injection. Dexamethasone administration increased the activity of fetal lung choline-phosphate cytidylyltransferase by 34%. It had no effect on the activities of fetal lung choline kinase and choline phosphotransferase. Exposure of fetal lung type II cells in organotypic cultures (which contain both type II cells and fibroblasts) to cortisol resulted in a 1.6-fold increase in the incorporation of [Me-3H]choline into saturated phosphatidylcholine. The activities of the enzymes in the choline pathway for the de novo biosynthesis of phosphatidylcholine were not significantly altered except for a 105% increase in choline-phosphate cytidylyltransferase activity. Treatment of monolayer cultures of fetal type II cells with cortisol-conditioned medium from fetal lung fibroblasts resulted in a 1.5-fold increase in saturated phosphatidylcholine production. This effect correlated with a doubling of choline-phosphate cytidylyltransferase activity. Additional evidence that this stimulatory action is mediated by fibroblast-pneumonocyte factor, produced by fetal lung fibroblasts in response to cortisol, was obtained. The factor was partially purified from cortisol-conditioned medium of fetal lung fibroblasts by gel filtration and affinity chromatography. Based on biological activity, a 3000-fold purification was obtained. Stimulation of saturated phosphatidylcholine synthesis in type II cells by fibroblast-pneumonocyte factor was maximal within 60 min of incubation. Pulse-chase experiments indicated that the stimulatory effect was correlated with an increased conversion of choline phosphate into CDP choline. Moreover, the enhanced phosphatidylcholine formation by fetal type II cells in response to fibroblast-pneumonocyte factor was accompanied by decreased levels of cellular choline phosphate. These findings further support the concept that glucocorticoid action on surfactant-associated phosphatidylcholine synthesis occurs ultimately at the level of the alveolar type II cell and involves fibroblast-pneumonocyte factor which stimulates the activity of choline-phosphate cytidylyltransferase.

Animals↗

PubMed1986

Alveolar macrophage stimulation of lung fibroblast growth in asbestos-induced pulmonary fibrosis.

Asbestotic lesions are characterized by macrophagic accumulation, fibroblast proliferation, and collagen deposition. To evaluate the potential involvement of alveolar macrophages in the subsequent fibrogenic reaction, the authors studied the effects of macrophages from normal and asbestos-treated rats upon lung fibroblast proliferation in vitro. Culture supernatants from bronchoalveolar (BAL) cells (99% macrophages) of normal rats stimulated lung fibroblast DNA synthesis and growth in a dose-dependent manner. Fibroblast growth factor (FGF) release by alveolar macrophages (AMs) was rapid (within 1 hour of incubation) and dependent on the number of AMs in culture. Moreover, culture supernatants from BAL cells of animals exposed to asbestos (single intratracheal injection) stimulated fibroblast proliferation to a greater degree than culture supernatants from BAL cells of control animals. Enhanced FGF production occurred 1 week after asbestos instillation and persisted up to 24 weeks. This change was accompanied in the early stages (1-4 weeks) by an increase in the total number of BAL cells which returned to control values by 12 weeks. Differential analysis of BAL cell populations showed a transient infiltration of neutrophils in the bronchoalveolar compartment followed by a significant accumulation of macrophages which persisted up to 1 month. Furthermore, lungs of asbestos-treated animals showed evidence of pathologic alterations characterized by fibroblast proliferation and collagen deposition. This study demonstrates that increased production of fibroblast growth factor by alveolar macrophages in vitro coincides with the development of asbestos-induced fibrosis. Prolonged stimulation of FGF release may contribute to excessive fibroblast proliferation and fibrosis.

Animals↗

PubMed1994

Involvement of calcium channels in fibroblast growth factor-induced activation of arterial cells in spontaneously hypertensive rats.

To gain insight into the mechanisms that could account for the abnormal vascular structure in spontaneously hypertensive rats (SHR) and to determine whether this could be affected by calcium channel blockers, we compared the influence of dihydropyridines on basic fibroblast growth factor (bFGF)-induced DNA synthesis in cultured adventitial fibroblasts isolated from SHR and Wistar-Kyoto rat (WKY) aorta. Our results showed that (a) bFGF was a potent mitogen for adventitial fibroblasts, much more active in SHR-derived than in WKY-derived cells, thus confirming the hyperreactivity of the SHR arterial cells; (b) the mitogenic potency of bFGF could be reduced by dihydropyridines (rank order of potency was nifedipine approximately nisoldipine > nitrendipine > nimodipine); and (c) the nifedipine inhibitory effect could be completely and partially antagonized in WKY- and SHR-derived fibroblasts, respectively, by the calcium channel agonist Bay K 8644. Moreover, the extent of nifedipine inhibitory extent increased and decreased in SHR- and WKY-derived fibroblasts, respectively, according to duration of treatment of cells with the drug, suggesting that SHR fibroblasts became progressively more sensitive whereas those of WKY became more refractory to the drug treatment. These data indicate that in aortic fibroblasts stimulated by bFGF, L-type calcium channels participate in the antimitotic effect of dihydropyridines and suggest the existence of interactions between these channels and the bFGF signaling pathways. They also suggest that nifedipine inhibits bFGF-induced DNA synthesis by different mechanisms in SHR and WKY fibroblasts.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1996

A natural kinase-deficient variant of fibroblast growth factor receptor 1.

A fibroblast growth factor receptor 1 variant missing 37 amino acids from the carboxy-terminal tyrosine kinase catalytic domain was discovered in human lung fibroblasts and several other human cell lines. The receptor variant binds specifically to acidic fibroblast growth factor but has no tyrosine kinase activity. It was found that cellular transfectants expressing the fibroblast growth factor receptor 1 variant are mitogenically inactive and ligand binding to the receptor causes neither receptor autophosphorylation nor phospholipase C-gamma transphosphorylation. The fibroblast growth factor receptor 1 variant therefore represents an inactive receptor for acidic fibroblast growth factor. Since both kinase and kinase-deficient receptor forms are expressed in cells, it is conceivable that the kinase-deficient receptor plays an important role in regulating cellular responses elicited by acidic fibroblast growth factor stimulation.

Base Sequence↗

PubMed1997

Keratinocyte growth factor mRNA expression in periodontal ligament fibroblasts.

Keratinocyte growth factor (KGF) is a fibroblast growth factor which mediates epithelial growth and differentiation. KGF is expressed in subepithelial fibroblasts, but generally not in fibroblasts of deep connective tissue, such as fascia and ligaments. Here we demonstrate that KGF mRNA is expressed in periodontal ligament fibroblasts, and that the expression is increased upon serum stimulation. Fibroblasts from human periodontal ligament, from buccal mucosa, from gingiva, and from skin were established from explants. Alkaline phosphatase activity was used as an indicator of the periodontal nature of fibroblasts. Cells were first cultured in DMEM with 0.5% fetal calf serum (FCS) and then incubated for 8 h, and 72 h in fresh DMEM with 10% FCS. Total RNA was isolated and used for Northern blotting with a P32-labeled KGF cDNA probe. Total RNA from cultured keratinocytes was used as negative controls. KGF mRNA was found in all cultured fibroblasts. Upon addition of 10% FCS to the cell cultures, an increase in KGF mRNA levels was noticed especially after 72 h. Furthermore, RT-PCR analysis of material scraped from the tooth root surface indicated the presence of KGF mRNA even in noncultured periodontal ligament cells.

Adolescent↗

PubMed2003

Impact of transplanted fibroblasts on rabbit skin wounds.

OBJECTIVES: To determine the effect of injected fibroblasts on full-thickness cutaneous wounds and to distinguish between the properties of fetal vs adult fibroblasts. DESIGN: Full-thickness cutaneous wounds were created by incision in the skin of adult New Zealand white rabbits and treated with fluorescently labeled autogenic, allogenic, and xenogenic fetal and adult fibroblasts. Wound healing was evaluated by histologic analysis and tensiometry over time. SUBJECTS: A total of 9 New Zealand white rabbits with 24 wounds per animal were examined in this study. Groups of 3 animals were treated with different fibroblasts and euthanized at 7, 14, and 28 days after manipulation. INTERVENTION: Fibroblasts were labeled with a fluorescent dye (CM-DiI) and suspended in a hyaluronic acid gel. The cell-gel mix was used to treat full-thickness incisional wounds in rabbit skin. Imaging of CM-DiI determined the quantity and the migratory patterns of the transplanted fibroblasts present in the wounds. Tensiometry characterized the mechanical properties of the healed connective tissue. RESULTS: Transplanted fibroblasts exhibited good survival and migration patterns. Cell therapy increased the tensile strength of the wounds. Allogenic fetal and autogenic adult fibroblasts achieved similar effects. CONCLUSIONS: Cell therapy is a viable approach to significantly affect the course of normal cutaneous wound healing, and cell lines from genetically unrelated donors do not appear to be disadvantaged by a host immune response compared with autogenic cell lines.

Animals↗

PubMed1996

Fibroblast growth factor-induced motor end plate regeneration in atrophic muscle.

OBJECTIVE: To determine whether fibroblast growth factor 1 implanted with viable nerve into atrophic muscle will stimulate formation of functional, acetylcholine producing motor end plates. DESIGN: Twelve male Lewis rats underwent predenervation of the hamstring muscle 8 weeks before implantation of the nerve at a site distant from the original motor end plate. Six animals underwent implantation of the tagged nerve ending into atrophic muscle with 50 microgram of fibroblast growth factor 1 in a fibrin adhesive carrier (group 1). Three animals underwent implantation with nerve, fibrin adhesive, and no fibroblast growth factor 1 (group 2); and three animals underwent implantation with fibroblast growth factor 1 and fibrin adhesive with no nerve (group 3). Animals were killed 9 weeks after implantation and nerve and muscle specimens were harvested. MAIN OUTCOME MEASURES: Histoenzymologic methods for acetylcholinesterase and silver impregnation of nerve fibers were performed 9 weeks after fibroblast growth factor 1-fibrin adhesive implantation. Variables included the number of motor end plates per highpower field and motor end plate length. RESULTS: Robust axonal sprouting and formation of multiple motor end plates were found arborized in serial fashion equidistant around the implanted nerve ending. Rare extrasynaptic staining occurred. End plate lengths were significantly shorter in the fibroblast growth factor 1-treated muscles (group 1) than in the specimens without fibroblast growth factor 1 (group 2) (31.2 vs 58.5 micron; P>001, paired t test). The arborization of motor end plates, rare extrasynaptic staining, and shorter end plate lengths seen in group 1 were all consistent with mature motor end plates. Controls (group 3) displayed limited motor end plate formation and extensive extrasynaptic staining typical of denervation. CONCLUSION: This study presents encouraging evidence that fibroblast growth factor 1 with fibrin adhesive carrier can facilitate the reinnervation of atrophied muscle by enhancing the formation or revitalization of motor end plates. Future studies will address muscle function and use of different carrier materials.

Animals↗