A three‐dimensional skin equivalent reflecting some aspects of <i>in vivo</i> aged skin

Diekmann, Johanna; Alili, Lirija; Scholz, Okka; Giesen, M; Holtkötter, Olaf; Brenneisen, Peter

doi:10.1111/exd.12866

Cited by 43 publications

(44 citation statements)

References 59 publications

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“…Therefore, these findings highlight the importance that the presence of keratinocytes and a 3D environment has on the behaviour of SD‐HDF. In fact, in agreement with our findings, it has been recently found that co‐cultures of keratinocytes and fibroblasts from aged donors in collagen dermal substrates are a very useful alternative to in vivo studies and that epithelial‐dermal interactions play an important role in the skin ageing process, so that a 3D model would be needed for its proper study.…”

Section: Discussionsupporting

confidence: 91%

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks

Pérez-Aso¹,

Roca²,

Bosch³

et al. 2019

Intern J of Cosmetic Sci

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Objective Stretch marks are disfiguring skin lesions that often cause problems of self‐esteem, but little effort has been put to studying this pathology. We therefore analysed cell cultures of dermal fibroblasts isolated from a striae albae, to thereafter reconstruct a full thickness skin model. Methods Human Dermal Fibroblasts (HDF) were isolated from a striae distensae (SD) lesion and from the adjacent non‐lesioned skin. The dermis of two full thickness skin models was reconstructed with either striae‐ or normal‐HDF, while the epidermis was in both reconstructed with Normal Human Epidermal Keratinocytes. Results Main observations and pertinent data: Gene expression analysis of cell cultures revealed a generalized decomposition of the Extra Cellular Matrix (ECM), since collagens type I and III, lysyl oxidase (LOX), biglycan, lumican and fibronectin were downregulated, while MMP3 was increased together with a decrease of its natural inhibitors (TIMP1, TIMP2 and PAI‐1). These findings were statistically corroborated for key ECM elements at the protein level (COL1, MMP1 and TGFB1). Interestingly, striae albae fibroblasts retained a pro‐inflammatory phenotype, as suggested by increased gene expression of CXCL8, HAS1 and TNFA. We next reconstructed a full thickness skin model (Striae Reconstructed) with dermal fibroblasts from striae albae. Gene expression analysis showed that the Striae Reconstructed elicited not only ECM decomposition, but also skin ageing, as indicated by the upregulation of P16, PTGS2 and SOD2. Discussion points: Although the epidermis was constructed with normal human epidermal keratinocytes, the Striae Reconstructed presented epidermal atrophy and a dramatic increase of β1‐integrin at the epidermal‐dermal junction providing, for the first time to our knowledge, a rationale showing that the key cell player behind stretch marks are dermal fibroblasts rather than epidermal keratinocytes. Conclusion New knowledge: Taken together, our findings shed new light into the aetiology of stretch marks and indicate that the Striae Reconstructed, a new model for in vitro testing and drug screening, may open new avenues for the treatment of stretch marks.

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Section: Discussionsupporting

confidence: 91%

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks

Pérez-Aso¹,

Roca²,

Bosch³

et al. 2019

Intern J of Cosmetic Sci

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“…Original studies employing alternative methods have been frequently published in Experimental Dermatology in the last years . In line with this tradition, the present special issue also showcases a number of original contributions, which can be viewed as current examples for new developments in alternative methods.…”

mentioning

confidence: 54%

The 3R approach to experimental dermatology

Schneider

Pincelli

2018

Experimental Dermatology

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“…From the 1980s, a simple 3D skin culture comprising keratinocytes cultured on a nylon mesh carrier began to be used for evaluating the safety of cosmetics and daily consumables . Currently, 3D reconstructed skin is widely used for skin ageing research . Various improved models are commercially available from a variety of suppliers (Table ).…”

Section: Skin Ageing Researchmentioning

confidence: 99%

“…[30,31] Currently, 3D reconstructed skin is widely used for skin ageing research. [32,33] Various improved models are commercially available from a variety of suppliers (Table 1) corrosion test, [34] and TG439, a skin irritation test. [35] On the other hand, 3D skin models are not allowed to be used for drug penetrance or permeability assays.…”

Section: D Culturementioning

confidence: 99%

Alternative test models for skin ageing research

Nakamura

Haarmann‐Stemmann

Krutmann

et al. 2018

Experimental Dermatology

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Increasing ethical concerns regarding animal experimentation have led to the development of various alternative methods based on the 3Rs (Refinement, Reduction and Replacement), first described by Russell and Burch in 1959. Cosmetic research and skin ageing research are particularly susceptible to concerns related to animal testing. In addition to animal welfare reasons, there are scientific and economic reasons to reduce and avoid animal experiments. Importantly, animal experiments may not reflect findings in humans mainly because of the differences in architectures and immune responses between animal skin and human skin. Here, we review the shift from animal testing to the development and application of alternative non-animal-based methods and the necessity and benefits of this shift. Some specific alternatives to animal models are discussed, including biochemical approaches, 2-dimensional and 3-dimensional cell cultures and volunteer studies, as well as future directions, including genome-based research and the development of in silico computer simulations of skin models. Among the in vitro methods, 3-dimensional reconstructed skin models are highly popular and useful alternatives to animal models however still have many limitations. With careful selection and skilful handling, these alternative methods will become indispensable for modern dermatology and skin ageing research.

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A three‐dimensional skin equivalent reflecting some aspects of in vivo aged skin

Cited by 43 publications

References 59 publications

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks

Striae reconstructed, a full thickness skin model that recapitulates the pathology behind stretch marks

The 3R approach to experimental dermatology

Alternative test models for skin ageing research

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