SEARCH · PubMed Health

Results for “Myofibroblasts”

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 19 recordsLinked to original sources

PubMed2026

Low-Grade Myofibroblastic Sarcoma Represents an Epigenetically Distinct Myofibroblastic Tumor With USP6 Upregulation and Stable Genome.

Low-grade myofibroblastic sarcoma (LGMS) is a rare, indolent mesenchymal neoplasm exhibiting myofibroblastic differentiation, with a propensity for local recurrence. The molecular basis of LGMS and its precise relationship with other histological mimics have remained largely undefined. To address this gap, we conducted the first comprehensive multiomics analysis of 6 LGMS cases, integrating whole-exome sequencing, RNA sequencing, and Illumina Methylation EPICv2 array profiling with comparative analysis against public sarcoma methylation cohorts and related fibroblastic tumors. Clinically, patients (median age 35.5 years) presented with small tumors (median size 1.45 cm), predominantly located in the head and neck, displaying classic histological features of diffusely infiltrative spindle cell fascicles with patchy mononuclear inflammation. Two of the 5 patients with follow-up developed local recurrence, and none metastasized (median follow-up duration 92.5 months). Genomically, all LGMS exhibited a low tumor mutational burden (median 2.31 mut/Mb) and a minimal fraction of genome altered, with TP53 and TSC2 deletions and NTRK1 and ERBB3 amplifications found in a subset of cases. No pathogenic fusions were detected. Transcriptomic profiling revealed a distinct signature featuring prominent USP6 overexpression and upregulation of inflammatory and immune-related genes, including CD274 (PD-L1), and enrichment of inflammatory and interferon-gamma response signatures. Epigenetically, LGMS formed a unique methylation cluster closest to inflammatory myofibroblastic tumor, with numerous differentially methylated regions and higher immune infiltration, particularly monocytes, compared with other fibroblastic tumors. These findings establish LGMS as a genomically stable, epigenetically distinct myofibroblastic sarcoma driven by USP6 overexpression and an inflammation-enriched transcriptome. They support its recognition as a standalone entity, facilitate integration into methylation-based sarcoma classifiers for improved diagnostic precision, and nominate USP6-associated pathways and immune checkpoint blockade as promising therapeutic strategies for recurrent or unresectable disease.

Humans↗

PubMed1989

Comparative growth dynamics and actin concentration between cultured human myofibroblasts from granulating wounds and dermal fibroblasts from normal skin.

The normal contraction of open wounds and many forms of pathologic contracture are related by the presence of a contractile fibroblast known as a myofibroblast. The function of this cell has been postulated as a result of previous pharmacological, immunological, and biochemical testing on strips of contracted connective tissue. The purpose of this study was to develop a specific assay that could measure the concentration of one contractile element (actin) within cultured myofibroblasts isolated from a contracting wound and in normal fibroblasts from uninjured dermis. Rates of growth and actin concentration through 15 days of culture were compared among populations of paired control fibroblasts from normal dermis and granulating wound myofibroblasts from three patients. Growth curves showed that myofibroblasts always grew slower than fibroblasts. An enzyme-linked immunosorbent assay showed that actin concentration was generally greater in mass cultures of granulating wound myofibroblasts than in fibroblasts from uninjured dermis. During exponential growth (1-6 days) the average actin concentration among myofibroblast lines ranged from 24 to 62 pg/cell. Average actin levels among control fibroblasts ranged from 3 to 47 pg/cell during the same interval. After 15 days of culture, actin concentration peaked twice. The first actin peak occurred within the period of exponential growth. At confluency, cellular actin levels dropped. Superconfluent cultures exhibited a second actin peak that displayed an irregular pattern of actin concentration. The latter observation suggested an artifact that might be the result of three-dimensional matrix of cells that altered points of cell adhesion and produced an irregular pattern of actin concentration. These data show that the phenotype of increased actin in cultured myofibroblasts was carried over by myofibroblasts from contracted skin wounds to culture. Because of a higher concentration of actin in myofibroblasts than in undifferentiated fibroblasts, these data suggest that the differentiation process of myofibroblasts may be associated with an increased availability of monomeric actin for filament synthesis. This study demonstrates that the use of tissue culture and our enzyme-linked immunosorbent assay will be a useful method to study factors affecting myofibroblast phenotypic modulation. Future studies should be directed toward developing procedures for isolation of pure populations of myofibroblasts as well as extracellular matrices that would maintain the morphology of both differentiated myofibroblasts and normal undifferentiated fibroblasts.

Actins↗

PubMed1992

Identification, paracrine generation, and possible function of human breast carcinoma myofibroblasts in culture.

Myofibroblasts from human breast carcinomas were identified and experimentally generated in culture, and a possible function was examined. The frequency of alpha-smooth muscle actin immunoreactive cells was evaluated as a measure of myofibroblast differentiation in primary culture. Few or no alpha-smooth muscle actin-positive stromal cells (6.1 +/- 8.4%) were identified in primary cultures from normal breast tissue (n = 9). In contrast, high frequencies (68.8 +/- 15.1%) were observed in primary cultures from carcinomas (n = 19). The frequencies of myofibroblasts in primary cultures were almost identical to those obtained in the corresponding cryostat sections (69.1 vs. 68.8%). A possible precursor cell to the myofibroblast was looked for among typical fibroblasts and vascular smooth muscle cells. Purified blood vessels containing both fibroblasts and vascular smooth muscle cells were embedded in collagen gel and incubated with medium conditioned by breast epithelial cells. Fibroblasts rather than smooth muscle cells were recruited from the blood vessels. In medium conditioned by carcinoma cell lines or in co-cultures of carcinoma cell lines and purified fibroblasts, alpha-smooth muscle actin and the typical myofibroblast phenotype were induced in otherwise alpha-smooth muscle actin-negative fibroblasts. The effect of myofibroblasts on cellular movement--essential to neoplastic cells--was analyzed. Spontaneous motility of tumor cells (MCF-7) was entirely suppressed in a collagen gel assay. Under these conditions tumor cell motility was selectively mediated by direct cell-to-cell interaction between tumor cells and myofibroblasts. Under chemically defined conditions, interaction was dependent on the presence of plasminogen. Anti-plasminogen, soybean trypsin inhibitor, and anti-fibronectin partly neutralized the effect of plasminogen. It is concluded that elements of myofibroblast differentiation and function may be studied in culture.

Actins↗

PubMed1979

Inhibition of myofibroblasts by skin grafts.

The myofibroblast population was studied by electron microscopy in rat wounds healing by (1) contraction of granulation tissue, (2) by coverage with split-skin grafts, and (3) by coverage with full-thickness skin grafts. In all 3 types of wounds, myofibroblasts appeared early and reached a peak number at two weeks after wounding. At this time, 40 to 50 percent of the wound fibroblasts had myofibroblast characteristics. The granulating wounds contracted rapidly and completely, and had long persistence of myofibroblasts. Split-skin grafted wounds contracted less and had a more rapid decrease in myofibroblasts. The wounds covered with full thickness skin grafts had a minimum of contraction with a very rapid decrease in the number of myofibroblasts until by 4 weeks no myofibroblasts were present. Full-thickness skin grafts thus appeared to influence contracting wounds not by preventing the formation of myofibroblasts, but by speeding up completion of their life cycle.

Animals↗

PubMed1992

Intracellular actin as a marker for myofibroblasts in vitro.

BACKGROUND: Myofibroblasts are found in a wide variety of normal tissues and pathological conditions. It is suggested that myofibroblasts are derived from normal fibroblasts and share with smooth muscle cells the expression of actin microfilament bundles. The aim of this study was to establish if the myofibroblast phenotype from tissue expander capsules and Dupuytren's nodules could be distinguished from normal dermal fibroblasts by quantitation of intracellular actin and the ratio of polymerized (filamentous) actin to nonpolymerized (globular) actin. EXPERIMENTAL DESIGN: Cell lines were established from six patients from each group. In addition to quantitation of intracellular actin, the cells were characterized by criteria of light microscopy, ultrastructure, actin immunofluorescence, and growth rates. RESULTS: Dermal fibroblasts were the smallest and the most spindle-shaped but grew rapidly and had few actin microfilament bundles. By contrast, myofibroblasts from expander capsules were larger and more stellate, proliferated slowly, and had the most prominent microfilament arrays. Cells from Dupuytren's nodules were intermediate in phenotype. Substantial and significant differences in intracellular actin contents were found, ranging from 0.69 +/- 0.05 micrograms/10(4) cells in fibroblasts and 0.77 +/- 0.15 micrograms/10(4) cells for Dupuytren's nodule cells to 1.46 +/- 0.44 micrograms/10(4) cells in expander capsule myofibroblasts (p < 0.05). Similar findings were found with respect to ratios of fibroblast to globular actins, being 0.22 for fibroblasts and 0.38 for Dupuytren's nodule cells compared with 0.70 for expander capsule myofibroblasts (p < 0.01). CONCLUSIONS: Measurement of intracellular actin contents and fibroblast:globular actin ratios offers a rapid, sensitive, and reliable technique for establishment of the myofibroblast phenotype and has considerable advantages over traditional ultrastructural approaches for the study of myofibroblast differentiation/regression and in vitro responses to experimental manipulation.

Actins↗

PubMed1990

Instability of the myofibroblast phenotype in culture.

Myofibroblasts are cells that have features of both smooth muscle cells and fibroblasts. Myofibroblasts from rat granulation tissue were studied using a coordinated biochemical and morphological approach. These myofibroblasts were maintained in culture for more than 17 passages. After establishing that these cells were indeed myofibroblasts by immunohistochemical and ultrastructural criteria, their biochemical parameters and phenotypic stability were studied. Rat dermal fibroblasts grown under similar conditions served as controls. Biochemically, it was found that both cells produced similar types of procollagens, namely collagens I and III, in similar proportions at or near a 1:1 ratio. However, myofibroblasts at early passage produced threefold more procollagens than did fibroblasts at the same stage of passage, while similar quantities were produced in each at late passage. These observations for procollagens were confirmed by separate studies for collagens, as measured by hydroxyproline determinations. Such differences were also reflected ultrastructurally. Secretory vesicles were identified in myofibroblasts at early stage, but not at late stage of passaging. No such vesicles were seen in fibroblasts at any stage of passage. In conclusion, myofibroblasts are active secretory variants of fibroblasts which have an unstable phenotype in culture and become indistinguishable from fibroblasts at late passage.

Animals↗

PubMed1987

Development of capillary networks from rat microvascular fragments in vitro: the role of myofibroblastic cells.

A new model useful for studying capillary growth in vitro is described. When the microvessel fragments and accompanying single cells (myofibroblastic cells) from rat epididymal fat pads were co-cultivated, the myofibroblastic cells initially began to grow and reached confluence. A few days later, endothelial cells started to sprout from the vessel fragments, forming cellular cord networks on and in the multilayered myofibroblastic cells. Ultrastructurally, the lumina, surrounded by the endothelial cells having intercellular junctions, were observed at cross-sectioned cellular cords. The growth of cellular cords from the fragments always occurred after the myofibroblastic cells had reached confluence. The medium conditioned to isolated rat myofibroblastic cells stimulated not only the proliferation of the endothelial cells from the bovine capillary and human vein but also the migration of bovine capillary endothelial cells in vitro. Moreover, the extracellular matrix produced by rat myofibroblastic cells modulated the morphology of bovine capillary endothelial cells to a cordlike shape. These observations strongly suggest that the formation of the capillary in vitro is induced by myofibroblastic cells.

Animals↗

PubMed1992

The peritubular myofibroblasts in the testes from normal men and men with Klinefelter's syndrome. A quantitative, ultrastructural, and immunohistochemical study.

The ultrastructure and immunostaining with antibodies against actin, desmin, and vimentin were studied in the peritubular myofibroblasts of testes from normal men and men with Klinefelter' syndrome (KS). The seminiferous tubules were classified into five types (a-e), related to the progressive degree of sclerosis measured as thickening of the lamina propria. In control testes, only types a and b tubules were present, whereas the testes from men with KS showed types b, c, d, and e tubules. The ultrastructural study revealed abundant microfilament bundles with electron-dense bodies in the cell periphery of the myofibroblasts in a and b tubules. In c tubules, the microfilament bundles of the myofibroblasts were lacking in electron-dense bodies. Myofibroblasts in tubules d and e showed scanty microfilament bundles. Immunostaining of peritubular myofibroblasts with anti-actin antibodies was intense in tubule types a-c and scanty in types d and e. Immunostaining of myofibroblasts with anti-desmin antibodies was intense in tubule types a and b, and negative in types c-e. Immunostaining with anti-vimentin antibodies was weak in tubule types a-c and intense in types d and e. Quantitative study revealed that with the progression of sclerosis, the number and volume per cross-sectioned tubule of actin-containing cells and, mainly, desmin-containing cells decrease while the number and volume of vimentin-containing cells increase.

Actins↗

PubMedDate not supplied

Myofibroblast as a major cellular constituent of villous stroma in human placenta.

The human placenta requires contractile structures to generate energy for blood propulsion. Smooth muscle cells are not present in significant numbers in the human placenta while fibroblasts lack effective contractile properties. This study provides the following evidence that the stromal cells of the placental villi, cotyledonary septa and perivascular connective tissue are myofibroblasts. (I) Stromal cells are strongly positive for dipeptidylpeptidase IV (EC 3.4.14.5) which occurs exclusively in myofibroblasts as far as connective tissue cells are concerned. (2) The isoenzyme pattern of the placental dipeptidylpeptidase IV is identical to that of myofibroblasts in palmar fibromatosis on isoelectric focusing. (3) Antibodies raised against isolated placental dipeptidylpeptidase IV cross-react with dipeptidylpeptidase IV from myofibroblasts of palmar fibromatosis as shown by immunohistochemistry. (4) On electron microscopic examination, stromal cells present all the ultrastructural features of myofibroblasts. It is concluded that, except for the vascular component and a negligible number of Hofbauer cells, myofibroblasts make up nearly all the cellular constituents of human placental villous stroma.

Dipeptidyl Peptidase 4↗

PubMed1979

Myofibroblasts in the stroma of invasive and metastatic carcinoma: a possible host response to neoplasia.

After observing the presence of numerous stromal myofibroblasts in scirrhous mammary carcinomas, a series of invasive and metastatic carcinomas from diverse sites was examined by electron microscopy to determine whether myofibroblasts might also be present in their stroma. Myofibroblasts were identified in each instance and were most abundant in neoplasms which were hard, sclerotic, and retracted. This finding suggests that myofibroblasts represent a component of the stromal reaction to many carcinomas and contribute to the desmoplasia and retraction which characterize many of these neoplasms. The host commands several responses to neoplasia. As a result of the expression of tumor-associated antigens, the immune system contributes lymphocytes, macrophages, and antibodies, a reflection of immunologic surveillance against neoplasia. In contrast to experimental systems tumor neoantigens are poorly expressed or even lacking in many human neoplasms; thus, the immune system may be weakly stimulated or not activated at all. Tumor neovascularization induced by a tumor-angiogenesis factor represents a second host response, possibly deleterious, for it may facilitate tumor dissemination. The stromal myofibroblast reaction to many invasive and metastatic carcinomas may constitute a third, albeit more primitive response. The density of collagen produced and contractile state of such tissue may signify an attempt by the host stroma to contain the neoplasm and impede vascular invasion. If so, myofibroblast induction may complement immune surveillance or constitute a separate mechanism of response to invasive neoplasia in man.

Carcinoma↗

PubMed1991

The myofibroblast in Dupuytren's contracture.

Dupuytren's contracture nodules, but not cords, contain myofibroblasts. These cells, which combine many electron microscopic, physiologic, and immunohistochemical characteristics of fibroblasts and smooth muscle cells, are probably the active force of contraction. Prominent myofibroblasts and intracellular microtubules correlate with increased likelihood of clinical recurrence after surgery. Tissue culture of cells derived from Dupuytren's contracture myofibroblasts show consistently slower cell replication than from fibroblasts and show persistence of electron microscopic characteristics in early passages. Research in Dupuytren's contracture myofibroblasts has been done on human tissue and so has clinical correlation. Myofibroblast presence may help to predict recurrence of disease and suggests that palmar skin should be excised when adherent to disease nodules. The theory of myofibroblasts helps explain why the open technique often succeeds, and why full thickness skin grafts inhibit recurrent contracture.

Dupuytren Contracture↗

PubMed1992

Time-dependent appearance of myofibroblasts in granulation tissue of human skin wounds.

Human skin wounds (66) inflicted between 20 h and 7 months prior to biopsy were studied. In order to identify the type of cellular differentiation of the fibroblastic cells in the granulation tissue, alpha-smooth muscle actin and desmin were immunohistochemically localized. The value of any presumed time-dependent appearance and/or disappearance of positively stained cells was tested for the estimation of wound age. In skin specimens with a wound age less than 5 days (n = 15) no typical granulation tissue had developed and no alpha-actin-positive myofibroblasts could be detected. The first appearance of positively reacting myofibroblasts was noted in a 5-day-old wound. In 57% of the lesions with a wound age between 5 and 31 days (25 out of 44 cases) typical granulation tissue formation was present and myofibroblasts with positive reaction for alpha-smooth muscle actin could be identified. Numerous positively reacting cells could generally be found in wounds aged between 16 and 31 days, but also in wounds less than 16 days old. In 29% of the cases with a wound age of more than 31 days (2 out of 7 cases) alpha-sma-positive myofibroblasts also occurred. Fibroblastic cells positive for desmin could not be seen at all in our series. Our results demonstrate the appearance of alpha-sma-positive myofibroblasts with the initial formation of typical granulation tissue in human skin lesions as early as approximately 5 days after wounding. In contrast to recent experimental results these cells remained detectable in wounds aged more than 2 months in some cases.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation Studies as Topic↗

PubMed1976

Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study.

In granulation tissue produced in the rat by subcutaneous injection of turpentine oil or polyvynile sponge implantation, the great majority of fibroblasts (myofibroblasts) possess a contractile apparatus which makes them similar to smooth-muscle cells. Chemical analysis shows that these granulation tissues contain a high proportion of Type III collagen, a genetically distinct collagen normally associated with embryonic dermal tissue. Type III collagen may persist up to 9 months after sponge implantation and myofibroblasts are seen in granulation tissue by means of electron microscopy and immunofluorescence. When granulation tissue is resorbed 50 days after turpentine oil injection, myofibroblasts disappear and the dermis contains Type I collagen. The concurrent presence of myofibroblasts and Type III collagen suggests that myofibroblasts, in addition to their contractile activity, synthetize, at least in part, type III collagen.

Animals↗

PubMed1977

Occurrence of myofibroblasts in the different phases of morbus Dupuytren (Dupuytren's contracture).

Twenty-one surgically removed specimens of Morbus Dupuytren (M. D.) were studied by light and electron microscopy. The cell type observed in the proliferative phase shows the basic ultrastructural features of fibroblasts, while the majority of the cells in the involutional phase resemble myofibroblasts. Myofibroblasts exhibit ultrastructural characteristics of both smooth muscle cells and fibroblasts and are said to behave functionally like smooth muscle cells. In the residual phase, typical fibrocytes of connective tissue are found. These findings confirm the concept that fibroblasts are capable of converting into myofibroblasts and demonstrate the myofibroblasts represent an intermediate cell type of transitional cellular differentiation. The significance of myofibroblasts for the development of the contracture of M. D. is discussed.

Adult↗

PubMed1991

Myofibroblasts and myoepithelial cells in the chicken harderian gland.

An electron microscopic study of the myoepithelial cells in the chicken Harderian gland provides evidence that these cells can be transformed into myofibroblasts. After the application of a Brucella ovis suspension in sterile saline onto the eyeball, every 5 minutes for half an hour, myoepithelial cells gradually develop over a 90-minute period the characteristic features of myofibroblasts: bundles of intracytoplasmic microfilament; abundant rough endoplasmic reticulum; prominent Golgi complex; and surface membrane differentiations, that provide attachment to neighbouring epithelial cells. No typical desmosomes are observed. Besides, the intercellular space between epithelial cells and myofibroblasts increases and the basement membrane adjacent to myofibroblasts disappears. Hypoxia is hypothesized to be involved in the transformation of myoepithelial cells into myofibroblasts.

Actin Cytoskeleton↗

PubMed1991

Beta-D-xyloside induced modulations of glycosaminoglycans, proliferation, and cytoskeletal organization of rat liver myofibroblast-like cells (transformed fat storing cells).

Transformed fat storing cells, i.e. myofibroblast-like cells are the major source of proteoglycans in injured liver. In the present study p-nitrophenyl-beta-D-xylopyranoside (PNP-Xyl), a specific metabolic inhibitor of proteoglycan synthesis, was used to analyze some details of altered glycosaminoglycan metabolism, proliferation, morphology and cytoskeletal organization of myofibroblast-like cells (secondary cultures of fat storing cells) under conditions of abrogated proteoglycan synthesis. PNP-Xyl increased dose-dependently the synthesis of [35S] sulfate-labelled medium glycosaminoglycans, among which chondroitin sulfate formation was stimulated predominantly. The distribution and composition of glycosaminoglycans in the cellular and cell surface compartments were affected differently. Production of medium hyaluronan was reduced by more than 40% at 5 mM PNP-Xyl. The compound inhibited dose-dependently the mitotic activity of myofibroblast-like cells without affecting viability. The morphologic appearance was changed at 5 mM PNP-Xyl and the organization and expression of desmin and smooth muscle iso-alpha-actin, both important markers of myofibroblast-like cells, were also modified by PNP-Xyl. Inhibition of proliferation, morphologic changes, and cytoskeletal disorganization were fully and rapidly reversible upon removal of the drug. The results support the notion of a direct or indirect role of proteoglycans in maintaining important functions of myofibroblast-like cells in culture.

Adipose Tissue↗

PubMed1990

Helium-neon laser treatment transforms fibroblasts into myofibroblasts.

The differentiation of myofibroblastic cells from normal human gingival fibroblasts in vitro has been established by transmission electron microscopy and quantitated by immunohistochemistry, using antigelsolin monoclonal antibodies. Untreated control cultures were compared to cultures exposed to Helium-Neon (He-Ne) laser irradiation. A direct and massive transformation of the cultured fibroblasts into myofibroblasts was observed as early as 24 hours after laser treatment, whereas control cultures were comprised of only resting fibroblasts and active fibroblasts. This in vitro induction of myofibroblasts may be analogous to that which occurs in vivo. Therefore we undertook a similar study using biopsies from gingival tissues after wisdom tooth extraction. Myofibroblasts were present in the connective tissue of laser-treated gums 48 hours after irradiation, but not in untreated contralateral control tissues. These data provide evidence that the primary biologic effect of the Helium-Neon laser on connective tissue is the rapid generation of myofibroblasts from fibroblasts. The induction of a phenotype with contractile properties may have clinical significance in the acceleration of the wound-healing process.

Actins↗

PubMed1989

Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins.

We examined by immunofluorescence the distribution of vimentin, desmin, alpha-smooth muscle actin and alpha-sarcomeric actin in normal human soft tissues and in pathologic tissues containing myofibroblasts, including normally healing granulation tissue, hypertrophic scar, and fibromatosis. The pattern of actin isoforms was also documented biochemically by two-dimensional gel electrophoresis. Fibroblastic and/or myofibroblastic cells in each setting always expressed vimentin and never alpha-sarcomeric actin. Moreover, these cells showed an heterogeneous cytoskeletal composition which defined four phenotypes: (a) cells expressing only vimentin; (b) cells expressing vimentin, alpha-smooth muscle actin and desmin; (c) cells expressing vimentin and alpha-smooth muscle actin; and (d) cells expressing vimentin and desmin. Given this, two groups of lesions are distinguished: the first contains only vimentin cells and consists of normally healing granulation tissue, eschars and normally healed scars; the second contains vimentin cells admixed with variable proportions of vimentin, alpha-smooth muscle actin and desmin, vimentin and alpha-smooth muscle actin, and vimentin and desmin cells and consists of hypertrophic scars and fibromatoses. Immunogold electron microscopy showed that alpha-smooth muscle actin was present in a proportion of cells with ultrastructural features of myofibroblasts. Our findings suggest that contrary to myofibroblasts of normally healing granulation tissue and normally healed scars, myofibroblasts of pathologic conditions characterized by chronic retraction express always immunochemical features indicative of smooth muscle differentiation.

Actins↗