Establishment of a 2-week canine skin organ culture model and its pharmacological modulation by epidermal growth factor and dexamethasone

The skin is a passive and active barrier which protects the body from the environment. Its health is essential for the accomplishment of this role. Since several decades, the skin has aroused a strong interest in various fields (for e.g. cell biology, medicine, toxicology, cosmetology, and pharmacology). In contrast to other organs, 3D models were mostly and directly elaborated in humans due to its architectural simplicity and easy accessibility. The development of these models benefited from the societal pressure to reduce animal experiments. In this review, we first describe human and mouse skin structure and the major differences with other mammals and birds. Next, we describe the different 3D human skin models and their main applications. Finally, we review the available models for domestic animals and discuss the current and potential applications.

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“…[22,144]). Two canine skins explant models which could be maintained viable for 2 weeks were recently published [133,145].…”

Section: Skin Explants In Animalsmentioning

confidence: 99%

3D skin models in domestic animals

Souci

Denesvre

2021

Vet Res

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“…Indeed, animal skin models are needed for the development of pharmaceutical and cosmetic products for veterinary use, yet there are no canine skin equivalents commercially available. Although, some methodologies were described to maintain canine skin biopsies in culture [11,12], to isolate dermal fibroblasts and keratinocytes and to obtain a 3D multilayer epidermis using natural canine skin explants [4,13,14], there is a lack of an easily standardizable methodology using culture-developed canine epidermis to test the efficacy and the biosafety of veterinary products. Thus, the aim of this study was to develop a canine epidermis analog based on CPEK (canine progenitor epithelial keratinocytes) expansion and differentiation in culture at the air-liquid surface.…”

Section: Introductionmentioning

confidence: 99%

cEpiderm, a Canine Skin Analog Suitable for In Vivo Testing Replacement

Marques

Nunes

Ustymenko

et al. 2022

BioChem

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Skin is one of the organs most tested for toxicity and safety evaluation during the process of drug research and development and in the past has usually been performed in vivo using animals. Over the last few years, non-animal alternatives have been developed and validated epidermis models for human and rat skin are already available. Our goal was to develop a histotypical canine skin analog, suitable for non-animal biocompatibility and biosafety assessment. Canine keratinocytes were seeded in an air-lift culture using an adapted version of the CELLnTEC protocol. Corrosion and irritation protocols were adapted from human EpiSkinTM. For histological analysis, sample biopsies were fixed in neutral-buffered formalin, and paraffin slices were routinely processed and stained with hematoxylin and eosin. A canine multilayer and stratified epidermal-like tissue (cEpiderm), confirmed by histological analysis, was obtained. The cEpiderm tissue exhibited normal morphological and functional characteristics of epidermis, namely impermeability and an adequate response to stressors. The cEpiderm is a promising canine skin model for non-animal safety testing of veterinary pharmaceuticals and/or cosmetics, significantly contributing to reducing undesirable in vivo approaches. cEpiderm is therefore a valid canine skin model and may be made commercially available either as a service or as a product.

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“…Recognizing that re-epithelialisation and angiogenesis are key determinants of physiological cutaneous wound healing [10, 37, 40–42] we primarily assessed T4 effects on the regenerated epidermis (‘epithelial tongues’ [ET]) at the inner and outer edges of wounded skin fragments [7, 43] and on intradermal angiogenesis (see Fig 1). Re-epithelialisation can be instructively quantified by planimetric measurement of both the mean length (as an indicator of keratinocyte migration) and the combined areas of the inner and outer ET (as an indicator of total epithelial regeneration) [7] (Fig 1a–1g).…”

Section: Introductionmentioning

confidence: 99%

Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo

et al. 2019

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There is a pressing need for improved preclinical model systems in which to study human skin wound healing. Here, we report the development and application of a serum-free full thickness human skin wound healing model. Not only can re-epithelialization (epidermal repair) and angiogenesis be studied in this simple and instructive model, but the model can also be used to identify clinically relevant wound-healing promoting agents, and to dissect underlying candidate mechanisms of action in the target tissue. We present preliminary ex vivo data to suggest that Thyroxine (T4), which reportedly promotes skin wound healing in rodents in vivo , may promote key features of human skin wound healing. Namely, T4 stimulates re-epithelialisation and angiogenesis, and modulates both wound healing-associated epidermal keratin expression and energy metabolism in experimentally wound human skin. Functionally, the wound healing-promoting effects of T4 are at least partially mediated via fibroblast growth factor/fibroblast growth factor receptor-mediated signalling, since they could be significantly antagonized by bFGF-neutralizing antibody. Thus, this pragmatic, easy-to-use full-thickness human skin wound healing model provides a useful preclinical research tool in the search for clinically relevant candidate wound healing-promoting agents. These ex vivo data encourage further pre-clinical testing of topical T4 as a cost-efficient, novel agent in the management of chronic human skin wounds.

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Establishment of a 2-week canine skin organ culture model and its pharmacological modulation by epidermal growth factor and dexamethasone

Cited by 7 publications

References 41 publications

3D skin models in domestic animals

3D skin models in domestic animals

cEpiderm, a Canine Skin Analog Suitable for In Vivo Testing Replacement

Thyroxine (T4) may promote re-epithelialisation and angiogenesis in wounded human skin ex vivo

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