In VitroFibroplasia: Matrix Contraction, Cell Growth, and Collagen Production of Fibroblasts Cultured in Fibrin Gels

Tuan, Tai‐Lan; Song, Andrew; Chang, Stella; Younai, Soheil; Nimni, Marcel E.

doi:10.1006/excr.1996.0065

Cited by 180 publications

(147 citation statements)

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“…In culture, this was demonstrated at the protein and mRNA level, and in vivo by immunohistochemistry. 24,45 In normal skin, PAI-1 was present at low levels and associated with the vasculature, whereas in keloid tissue, PAI was dramatically increased and shifted to a fibroblast/territorial matrix localization. 24 In addition, we demonstrated that treatment of keloid fibroblasts with a PAI-1-specific polyclonal antibody reduced collagen synthesis to levels exhibited by normal fibroblasts.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, cell monolayers can be readily varied in size, permit rapid verification of experimental manipulations and retention of cells, and avoid the loss of cells from fibrin gels cultured under serum-free conditions. 45 Seven strains each of freshly isolated primary, first, or second passage fibroblasts from normal skin or keloids (Table 1) were cultured for 2 or 6 days in DMEM containing 0.1% ITSϩ, 3% FBS, or 10% FBS. The serum-free condition, ie, 0.1% ITSϩ, was used to reveal the inherent differences in PAI-1 expression and accumulation of newly synthesized collagen between normal and keloid fibroblasts; 3 and 10% FBS were used to determine the effects of serumderived growth factors.…”

Section: Increased Pai-1 and Collagen Are Reproducible Features Of Kementioning

confidence: 99%

“…24,45 Fibroblasts in fibrin gels were infected at 30, 100, and 300 moi with Ad-Wt PAI-1 or empty vector and subsequently cultured for 6 days in 3% FBS. These conditions avoid gel lysis by normal cells under lower serum conditions 45,46 and minimize possible effects of growth factors in higher serum concentrations. Ad-Wt PAI-1, but not empty vector, led to increased levels of PAI-1 protein in a viral dose-depen- dent manner ( Figure 4A).…”

Section: Overexpression Of Wild-type Pai-1 Protein In Normal Fibroblamentioning

confidence: 99%

“…RNA interference has been shown to be effective at decreasing PAI-1 expression and consequently increasing adherence in vascular endothelial cells 68 and suppressing replicative senescence. 69 It is not known, however, whether siRNA targeted to PAI-1 can be effective in dermal fibroblasts maintained for long periods of time in three-dimensional models of fibroplasia 45 and in diverse samples of keloid fibroblasts, using collagen synthesis as the outcome measure. Only when this has been demonstrated can investigations proceed to in vivo delivery tech-niques for eventual prophylactic treatment of patients at risk for keloid formation.…”

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confidence: 99%

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Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Tuan

Hwu

et al. 2008

The American Journal of Pathology

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Keloids are tumor-like skin scars that grow as a result of the aberrant healing of skin injuries, with no effective treatment. We provide new evidence that both overexpression of plasminogen activator inhibitor-1 (PAI-1) and elevated collagen accumulation are intrinsic features of keloid fibroblasts and that these characteristics are causally linked. Using seven strains each of early passage normal and keloid fibroblasts, the keloid strains exhibited inherently elevated collagen accumulation and PAI-1 expression in serumfree, 0.1% ITS؉ culture; larger increases in these parameters occurred when cells were cultured in 3% serum. To demonstrate a causal relationship between PAI-1 overexpression and collagen accumulation, normal fibroblasts were infected with PAI-1-expressing adenovirus. Such cells exhibited a two-to fourfold increase in the accumulation of newly synthesized collagen in a viral dose-dependent fashion in both monolayers and fibrin gel, provisional matrix-like cultures. Three different PAI-1-targeted small interfering RNAs, alone or in combination, produced greater than an 80% PAI-1 knockdown and reduced collagen accumulation in PAI-1-overexpressing normal or keloid fibroblasts. A vitronectin-binding mutant of PAI-1 was equipotent with wild-type PAI-1 in inducing collagen accumulation, whereas a complete protease inhibitor mutant retained approximately 50% activity. Thus, PAI-1 may use more than its protease inhibitory activity to control keloid collagen accumulation. PAI-1-targeted interventions , such as small interfering RNA and lentiviral short hairpin RNA-containing microRNA sequence suppression reported here , may have therapeutic utility in the prevention of keloid scarring.

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Section: Discussionmentioning

confidence: 99%

Section: Increased Pai-1 and Collagen Are Reproducible Features Of Kementioning

confidence: 99%

Section: Overexpression Of Wild-type Pai-1 Protein In Normal Fibroblamentioning

confidence: 99%

mentioning

confidence: 99%

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Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Tuan

Hwu

et al. 2008

The American Journal of Pathology

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“…9 Studies by other authors have also described a stimulatory effect of fibrin on ECM synthesis (mainly collagen I) by fibroblasts. 42,50 Collagen deposited on the membranes also enhanced adhesion, spreading, and proliferation of the cells, particularly of HaCaT keratinocytes. Collagen is a major component of ECM, and most of the cells bind to its oligopeptide sequence DGEA (Asp-Gly-Glu-Ala), mainly by α 2 β 1 or α 3 β 1 integrin receptors.…”

Section: Figure 11mentioning

confidence: 98%

Protein nanocoatings on synthetic polymeric nanofibrous membranes designed as carriers for skin cells

Bačáková¹,

Pajorová²,

Stránská³

et al. 2017

IJN

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Protein-coated resorbable synthetic polymeric nanofibrous membranes are promising for the fabrication of advanced skin substitutes. We fabricated electrospun polylactic acid and poly(lactide- co -glycolic acid) nanofibrous membranes and coated them with fibrin or collagen I. Fibronectin was attached to a fibrin or collagen nanocoating, in order further to enhance the cell adhesion and spreading. Fibrin regularly formed a coating around individual nanofibers in the membranes, and also formed a thin noncontinuous nanofibrous mesh on top of the membranes. Collagen also coated most of the fibers of the membrane and randomly created a soft gel on the membrane surface. Fibronectin predominantly adsorbed onto a thin fibrin mesh or a collagen gel, and formed a thin nanofibrous structure. Fibrin nanocoating greatly improved the attachment, spreading, and proliferation of human dermal fibroblasts, whereas collagen nanocoating had a positive influence on the behavior of human HaCaT keratinocytes. In addition, fibrin stimulated the fibroblasts to synthesize fibronectin and to deposit it as an extracellular matrix. Fibrin coating also showed a tendency to improve the ultimate tensile strength of the nanofibrous membranes. Fibronectin attached to fibrin or to a collagen coating further enhanced the adhesion, spreading, and proliferation of both cell types.

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Comparison of Growth Factor Expression in Fetal and Adult Fibroblasts

Broker¹,

Chakrabarti²,

Blynman³

et al. 1999

Arch Otolaryngol Head Neck Surg

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Background: Fetal wounds can heal without any histological evidence of scarring. Fetal wounds lack the inflammatory infiltrate characteristic of adult wounds, and the fetal environment is not necessary for scarless healing to occur. Recent evidence suggests that fibroblasts are the main effector of scarless healing in fetal tissue. What has not been shown is what profile of growth factors the fibroblast uses to influence wound repair.

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In VitroFibroplasia: Matrix Contraction, Cell Growth, and Collagen Production of Fibroblasts Cultured in Fibrin Gels

Cited by 180 publications

References 0 publications

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Adenoviral Overexpression and Small Interfering RNA Suppression Demonstrate That Plasminogen Activator Inhibitor-1 Produces Elevated Collagen Accumulation in Normal and Keloid Fibroblasts

Protein nanocoatings on synthetic polymeric nanofibrous membranes designed as carriers for skin cells

Comparison of Growth Factor Expression in Fetal and Adult Fibroblasts

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