Sprayed cultured autologous keratinocytes used alone or in combination with meshed autografts to accelerate wound closure in difficult-to-heal burns patients

James, Stuart; Booth, Simon; Dheansa, Baljit; Mann, Dawn J.; Reid, Michael; Shevchenko, Rostislav V.; Gilbert, Philip M.

doi:10.1016/j.burns.2008.11.011

Cited by 39 publications

(34 citation statements)

References 44 publications

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“…Original keratinocytes were cultured in 6-well culture dishes at a density of 110 4 /well. The original myofibroblastic differentiation medium consisted of nine volumes of complete Epilife medium and one volume of DMEM supplemented with 10% FBS.…”

Section: Keratinocyte-myofibroblast Transdifferentiation (Kmft) In VImentioning

confidence: 99%

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Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes

Han

et al. 2014

Sci. China Life Sci.

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Myofibroblasts, recognized classically by -smooth muscle actin (-SMA) expression, play a key role in the wound-healing process, promoting wound closure and matrix deposition. Although a body of evidence shows that keratinocytes explanted onto a wound bed promote closure of a skin injury, the underlying mechanisms are not well understood. The basal layer of epidermis is rich in undifferentiated keratinocytes (UKs). We showed that UKs injected into granulation tissue could switch into -SMA positive cells, and accelerate the rate of skin wound healing. In addition, when the epidermis sheets isolated from foreskin cover up the wound bed or are induced in vitro, keratinocytes located at the basal layers or adjacent sites were observed to convert into myofibroblast-like cells. Thus, UKs have a potential for myofibroblastic transition, which provides a novel mechanism by which keratinocyte explants accelerate skin wound healing. epithelial-mesenchymal transition, epithelial-myofibroblast transition, keratinocyte-myofibroblast transition, myofibroblast, wound healing Citation:Li MR, Ti DD, Han WD, Fu XB. Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes.

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Section: Keratinocyte-myofibroblast Transdifferentiation (Kmft) In VImentioning

confidence: 99%

“…Healing of these impaired wounds represents a challenge with currently available treatment. Cultured autologous keratinocytes have been used extensively to help treat these patients [2][3][4][5]. Autologous epidermal cell suspension transplantation seems to be an effective, simple and timesaving method to treat chronic non-healing wounds [6].…”

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confidence: 99%

Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes

Han

et al. 2014

Sci. China Life Sci.

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“…14,15 Furthermore, good correlation between outcomes in the Large White porcine model and human wound healing has been reported. 12,[16][17][18] Another advantage of this model is that due to its size, larger wounds can be created than in the other models. 19 This mimics more closely the clinical situation of a large burn.…”

Section: Wound Contraction In Animal Modelsmentioning

confidence: 99%

Strategies Demonstrating Efficacy in Reducing Wound ContractionIn Vivo

Sharpe

Martin

2013

Advances in Wound Care

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Significance: Scarring continues to present a significant clinical problem. Wound contraction leads to scarring and is mediated by myofibroblasts and contractile forces across the wound bed. Contracture formation can have a significant impact on the quality of life of the patient, particularly where function and appearance are affected. Recent Advances: Novel tissue-engineered matrices, cell-based therapies, and medicinal therapeutics have shown significant reduction in wound contraction in in-vivo models, particularly at early time points. These have been accompanied in many cases by reduced numbers of myofibroblasts, and in some by increased angiogenesis and improved neodermal architecture. Critical Issues: There are no animal models that replicate all aspects of wound healing as seen in patients. Therefore, information obtained from in vivo studies should be assessed critically. Additional studies, in particular those that seek to elucidate the mechanisms by which novel therapies reduce contraction, are needed to gain sufficient confidence to move into clinical testing. Future Directions: The use of knockout mouse models in particular has generated significant advances in knowledge of the mechanisms behind myofibroblast conversion and other factors involved in generating tension across the wound. Medicinal therapeutics and tissue-engineering approaches that seek to disrupt/alter these pathways hold much promise for future development and translation to clinical practice. SCOPEFull-thickness wounds heal with scarring, due to the abnormal arrangement of de novo collagen fibres in the neodermis and contractile forces exerted on the wound environment and surrounding tissue. Scar formation can have a negative impact on the patient and continues to present a significant clinical challenge. In vivo models take into account the physiological response to injury and the complex interactions that occur during wound repair that cannot be replicated in vitro. This review summarizes recent in vivo studies that have demonstrated efficacy in reducing wound contraction in model organisms. TRANSLATIONAL RELEVANCEThe demonstration of efficacy in vivo of a potential therapy to reduce wound contraction provides strong evidence of potential clinical efficacy. Further investigation and investment can then be undertaken to translate the novel therapy to early-stage clinical studies. In some cases, the manipulation, through the application of novel wound therapies, of the complex cascade of events leading to wound repair may have

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“…James at the Blonde McIndoe Centre, East Grinstead, UK (James et al 2010). The strains were obtained from 26 year old male patient (SK206AK) and 26 year old female Werner's syndrome patient (WSK368).…”

Section: Initiation and Culture Of Primary Human Keratinocytesmentioning

confidence: 99%

Absence of premature senescence in Werner's syndrome keratinocytes

Ibrahim

Sheerin

Jennert-Burston

et al. 2016

Experimental Gerontology

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Werner's syndrome (WS) is an autosomal recessive genetic disorder caused by loss of function mutation in wrn and is a useful model of premature in vivo ageing. Cellular senescence is a plausible causal mechanism of mammalian ageing and, at the cellular level, WS fibroblasts show premature senescence resulting from a combination of telomeric attrition and replication fork stalling. Over 90% of WS fibroblast cultures achieve less than 20 population doublings (PD) in vitro compared to wild type human fibroblast cultures.It has been proposed that some cell types, capable of proliferation, will fail to show a premature senescence phenotype in response to wrn mutations. To test this hypothesis, human dermal keratinocytes (derived from both WS and wild type patients) were cultured long term. WS Keratinocytes showed a replicative lifespan in excess of 100 population doublings but maintained functional growth arrest mechanisms based on p16 and p53. The karyotype of the cells was superficially normal and the cultures retained markers characteristic of keratinocyte holoclones (stem cells) including p63 expression and telomerase activity. Accordingly we conclude that, in contrast to WS fibroblasts, WS keratinocytes do not demonstrate slow growth rates or features of premature senescence. These findings suggest that the epidermis is amongst the tissue types that do not display symptoms of premature ageing caused by loss of function of wrn. This is in support that Werner's syndrome is a segmental progeroid syndrome.

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Sprayed cultured autologous keratinocytes used alone or in combination with meshed autografts to accelerate wound closure in difficult-to-heal burns patients

Cited by 39 publications

References 44 publications

Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes

Microenvironment-induced myofibroblast-like conversion of engrafted keratinocytes

Strategies Demonstrating Efficacy in Reducing Wound ContractionIn Vivo

Absence of premature senescence in Werner's syndrome keratinocytes

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