In vitro glycation of an endothelialized and innervated tissue-engineered skin to screen anti-AGE molecules

Cadau, Sébastien; Leoty-Okombi, Sabrina; Pain, Stéphanie; Bêchetoille, Nicolas; André-Frei, V.; Berthod, François

doi:10.1016/j.biomaterials.2015.01.066

Cited by 22 publications

(24 citation statements)

References 68 publications

(54 reference statements)

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“…To our knowledge, a skin model with a preglycated dermis compartment has been developed for antiglycation active screening purposes . In addition, an in vitro glycation model with an endothelial capillary and nerve system was engineered recently for studying glycation impact on microvasculature and sensory innervation in skin . Nevertheless, the application or use of both engineered skin models is tested with soluble drugs in culture media or preglycated dermis, but the robustness of the developed models to screen topical drug formulations is awaiting validation.…”

Section: Discussionmentioning

confidence: 99%

“…33,34 In addition, an in vitro glycation model with an endothelial capillary and nerve system was engineered recently for studying glycation impact on microvasculature and sensory innervation in skin. 35 Nevertheless, the application or use of both engineered skin models is tested with soluble drugs in culture media or preglycated dermis, but the robustness of the developed models to screen topical drug formulations is awaiting validation. In our present model, drug application by the topical route on the surface of the engineered skin model was proven, facilitating analyses of universal cosmeceutical and pharmaceutical formulations as well as the transepidermal penetration profile of numerous functional active ingredients.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Molecular characterization of glycation‐associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations

Lee¹,

Ng²,

Cheah

et al. 2016

Br J Dermatol

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Molecular characterization of glycation‐associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations

Lee¹,

Ng²,

Cheah

et al. 2016

Br J Dermatol

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“…Moreover, ribose not only produces structurally similar AGEs [ 18 ], but also reacts faster than glucose [ 19 ]. Nevertheless, the effects of glycation appear to depend on the glycation agent; with ribose and glyoxal being the most frequently used compounds [ 8 , 9 , 20 ]. Granted that aged skin is sufficiently perfused in vivo, the oxidative environment should favor glycation by sugars [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

“…Several nonclinical models of skin aging tried to emulate the long process of aging in vitro, by exposing juvenile reconstructed human skin (RHS) either to ribose, glyoxal, glyceraldehyde, or specific AGEs [ 6 , 7 , 8 , 9 , 10 ]. As the consequences of extracellular matrix (ECM) glycation depend on the stressor in vitro and strongly deviate among the protocols for RHS glycation, we were intrigued in the unknown effects of AGEs in RHS on epithelial proliferation and differentiation.…”

Section: Introductionmentioning

confidence: 99%

Ultrastructural and Molecular Analysis of Ribose-Induced Glycated Reconstructed Human Skin

Rigon

Kaessmeyer

Wolff

et al. 2018

IJMS

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Aging depicts one of the major challenges in pharmacology owing to its complexity and heterogeneity. Thereby, advanced glycated end-products modify extracellular matrix proteins, but the consequences on the skin barrier function remain heavily understudied. Herein, we utilized transmission electron microscopy for the ultrastructural analysis of ribose-induced glycated reconstructed human skin (RHS). Molecular and functional insights substantiated the ultrastructural characterization and proved the relevance of glycated RHS beyond skin aging. In particular, electron microscopy mapped the accumulation and altered spatial orientation of fibrils and filaments in the dermal compartment of glycated RHS. Moreover, the epidermal basement membrane appeared thicker in glycated than in non-glycated RHS, but electron microscopy identified longitudinal clusters of the finest collagen fibrils instead of real thickening. The stratum granulosum contained more cell layers, the morphology of keratohyalin granules decidedly differed, and the stratum corneum lipid order increased in ribose-induced glycated RHS, while the skin barrier function was almost not affected. In conclusion, dermal advanced glycated end-products markedly changed the epidermal morphology, underlining the importance of matrix–cell interactions. The phenotype of ribose-induced glycated RHS emulated aged skin in the dermis, while the two to three times increased thickness of the stratum granulosum resembled poorer cornification.

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“…Thus, the development of 3D organotypic culture models using primary human cells appears to be compelling. Various in vitro models depicting ageing have been described in the literature . Yet, very few have modelled the hormonal drop in human skin cells while focused on the IGF‐1R and within defined culture conditions.…”

Section: Introductionmentioning

confidence: 99%

In vitro epidermis model mimicking IGF‐1–specific age‐related decline

Mainzer

Remoué

Molinari

et al. 2018

Experimental Dermatology

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Ageing is a complex multifaceted process affecting skin functionality and structure. Several 3D organotypic skin culture models have reproduced ageing by inducing replicative senescence, glycation or oxidative stress. Yet, very few models have focused on hormonal ageing and especially the insulin-like growth factor 1 (IGF-1) signalling pathway, which has been associated with longevity in animal studies and is necessary for the early stages of skin development. In this study, we built an organotypic epidermis model with targeted IGF-1 receptor knockdown to reproduce some aspects of hormonal ageing on skin. Our model displayed morphological and functional features of aged epidermis, which were mostly attributed to a loss of function of the Stratum basale. IGF-1 receptor knockdown keratinocytes depicted an extended cell cycle, reduced proliferation potential and reduced adhesion capacities and greater sensitivity to oxidative stress than control cells. Altogether, this model represents an essential tool for further investigations into the mechanisms linked to some aspects of hormonal decline or when screening for potent anti-ageing compounds.

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In vitro glycation of an endothelialized and innervated tissue-engineered skin to screen anti-AGE molecules

Cited by 22 publications

References 68 publications

Molecular characterization of glycation‐associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations

Molecular characterization of glycation‐associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations

Ultrastructural and Molecular Analysis of Ribose-Induced Glycated Reconstructed Human Skin

In vitro epidermis model mimicking IGF‐1–specific age‐related decline

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