Fibrin Stimulates the Proliferation of Human Keratinocytes through the Autocrine Mechanism of Transforming Growth Factor-.ALPHA. and Epidermal Growth Factor Receptor

Yamamoto, Misa; Yanaga, Hiroko; Nishina, Hiromichi; Watabe, Shoji; Mamba, Koichi

doi:10.1620/tjem.207.33

Cited by 14 publications

(12 citation statements)

References 24 publications

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“…Similarly, we have confirmed that the primary effect of fibrin adhesive is to prevent run‐off even when using the diluted concentrations of fibrinogen and thrombin that are optimal for metabolic activity. Nevertheless, our findings also provide support for the theory that fibrin adhesive stimulates keratinocyte proliferation (Figures 5 and 6) and this concurs with recent reports from other groups 25,26 . We thus look forward to seeing further evaluation of our optimized procedure in animal and clinical trials.…”

Section: Discussionsupporting

confidence: 92%

Optimized delivery of skin keratinocytes by aerosolization and suspension in fibrin tissue adhesive

Harkin

Dawson

Upton

2006

Wound Repair Regeneration

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Aerosolized suspensions of keratinocytes provide a potential therapy for wounds, but the effects of aerosolization on cell viability remain unclear. Likewise, little is known of the resulting cell distribution pattern and how this compares to the density required for epithelialization. The potential benefits of cospraying cells in the presence of fibrin adhesive are equally uncertain. Thus, in the present study we have optimized conditions for the aerosolization of cultured keratinocytes using a device (Tissomat) that supports the option for coapplication with fibrin (Tisseel). Cell viability was unaffected when sprayed at 10 psi, but a significant reduction in metabolic activity, as determined by the methylthiazoyldiphenol-tetrazolium assay, was observed at higher pressure. Bursts of 0.2 mL cell suspension (1.5x10(6)/mL) delivered from a height of 10 cm was sufficient to epithelialize an area of 10-15 cm2 within 7 days in vitro. Confluent areas corresponded to those with a density of 5,000-10,000 cells/cm2 at 24 hours. Optimal cell growth in Tisseel was achieved through dilution of fibrinogen (1-3 mg/mL) and thrombin (2-5 IU/mL). This optimized formulation eliminated fluid run-off postspraying and stimulated a twofold increase in cellular response. Therefore, our in vitro data supports the theory that aerosolized suspensions of keratinocytes in fibrin will benefit healing.

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Section: Discussionsupporting

confidence: 92%

Optimized delivery of skin keratinocytes by aerosolization and suspension in fibrin tissue adhesive

Harkin

Dawson

Upton

2006

Wound Repair Regeneration

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“…In keratinocytes, fibrin stimulated the autocrine production of transforming growth factor alpha through the epidermal growth factor receptor. 47 Fibrin also partially restored the ability of senescent and growth-arrested human dermal fibroblasts to continue replicating. 48 However, after 2 weeks of cell cultivation, the cell proliferation (measured by cell metabolic activity) on membranes with fibrin became similar to the cell proliferation on the nonmodified membranes, which probably correlated with the degree of fibrin degradation.…”

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confidence: 93%

The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering

Bačáková¹,

Musı́lková²,

Riedel³

et al. 2016

IJN

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Fibrin plays an important role during wound healing and skin regeneration. It is often applied in clinical practice for treatment of skin injuries or as a component of skin substitutes. We prepared electrospun nanofibrous membranes made from poly( l -lactide) modified with a thin fibrin nanocoating. Fibrin surrounded the individual fibers in the membrane and also formed a thin fibrous mesh on several places on the membrane surface. The cell-free fibrin nanocoating remained stable in the cell culture medium for 14 days and did not change its morphology. On membranes populated with human dermal fibroblasts, the rate of fibrin degradation correlated with the degree of cell proliferation. The cell spreading, mitochondrial activity, and cell population density were significantly higher on membranes coated with fibrin than on nonmodified membranes, and this cell performance was further improved by the addition of ascorbic acid in the cell culture medium. Similarly, fibrin stimulated the expression and synthesis of collagen I in human dermal fibroblasts, and this effect was further enhanced by ascorbic acid. The expression of beta 1 -integrins was also improved by fibrin, and on pure polylactide membranes, it was slightly enhanced by ascorbic acid. In addition, ascorbic acid promoted deposition of collagen I in the form of a fibrous extracellular matrix. Thus, the combination of nanofibrous membranes with a fibrin nanocoating and ascorbic acid seems to be particularly advantageous for skin tissue engineering.

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“…However, after eight days of postinjury, patients with sepsis, large TBSA and non-survivors have had significantly lower values than those of non-septic, low TBSA and survivor group. Topical application of TGFα accelerates epidermal regeneration of partial thickness burn [51]. The burn-induced inflammation and inflammatory cytokines cause insulin resistance and hyperglycemia that are reflected on organ functions including liability to infection.…”

Section: Discussionmentioning

confidence: 99%

Pediatric burn and key regulatory cytokines: Impact of burn surface area and sepsis on the clinical outcomes

et al. 2010

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Burn is an injury which is not only devastating for the patients but also puts a great burden on the society by consuming enormous health care resources. Despite improvements in burn wound care and treatment, understanding the role of key pro-/anti-inflammatory cytokines in pathogenesis of burn injury, sepsis and survival requires clarification. This work aimed at measuring plasma levels of the following cytokines: leptin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-α, and basic fibroblast growth factor (bFGF), procalcitonin (PCT) and C-reactive protein (CRP) in children with thermal burn (n = 42; 22 males and 20 females with an age range of two months up to 7 years) vs. sex and age matched healthy controls (n = 26; 12 males and 14 females with an age range of six months up to 8 years). The venous samples were drawn from patients at 2nd and 8th day postinjury. The relationship between measured plasma cytokines with length of hospital stay, total burn surface area (TBSA), sepsis, survival and complete blood count were investigated. The fatality rate was 28.6% (n = 12). At the 2nd day of postinjury, burn cases showed significantly higher values of WBC, CRP, PCT, TNF-α, IL-6, leptin, bFGF, and TGF-α than healthy controls. At the 8th day of postinjury, sepsis caused further significant elevations of WBC, CRP, PCT, TNF-α and IL-6 levels but significantly lower TGF-α levels than cases without sepsis. At the 8th day of postinjury, patients with larger TBSA (> 30%) demonstrated significantly higher values of WBC, CRP, PCT, TNF-α, and IL-6, but significantly lower levels of bFGF and TGF-α than cases with smaller TBSA (≤ 30%). At the 8th day of postinjury, non-survivors showed significantly higher levels of WBC, CRP, PCT, TNF-α and IL-6, but significantly lower levels of leptin, bFGF, and TGF-α than survivors. Correlation studies showed significant positive correlation between TBSA and each of IL-6, TNF-α and leptin levels. Except for bFGF and TGF-α levels that were reduced, the increases in other parameters (PCT, TNF-α and IL-6) were directly proportionate to the burn severity, sepsis and fatality. Both bFGF and TGF-α correlated with poor prognostic burn healing in severe septic cases. PCT and/or IL-6 are valuable biomarkers for early detection of burn infections. TGF-α, bFGF and leptin being immuno- and angiogenic modulators might reduce inflammation and post-burn immune dysfunction and enhance burn healing.

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Fibrin Stimulates the Proliferation of Human Keratinocytes through the Autocrine Mechanism of Transforming Growth Factor-.ALPHA. and Epidermal Growth Factor Receptor

Cited by 14 publications

References 24 publications

Optimized delivery of skin keratinocytes by aerosolization and suspension in fibrin tissue adhesive

Optimized delivery of skin keratinocytes by aerosolization and suspension in fibrin tissue adhesive

The potential applications of fibrin-coated electrospun polylactide nanofibers in skin tissue engineering

Pediatric burn and key regulatory cytokines: Impact of burn surface area and sepsis on the clinical outcomes

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