Non-invasive bioluminescence imaging as a standardized assessment measure in mouse models of dermal inflammation

Hofmann, Martine; Schmidt, M.; Arne, Olga; Geißlinger, Gerd; Parnham, Michael J.; Bruin, Natasja de

doi:10.1016/j.jdermsci.2018.04.013

Cited by 5 publications

(1 citation statement)

References 51 publications

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“…Eight- to 12-week-old mice were subcutaneously injected with a methylcellulose-based gel (4% methylcellulose and 4.5% ammonium sulfate in phosphate-buffered saline (PBS) mixed 1:1 with protamine sulfate (0.25 mg ml −1 ), which forms a gel at body temperature 63 . A 27-gauge needle was used to inject the mice (100 µl).…”

Section: Methodsmentioning

confidence: 99%

Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation

Bernabé-Rubio,

Ali,

Bhosale

et al. 2023

Nat Cell Biol

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Dedifferentiation is the process by which terminally differentiated cells acquire the properties of stem cells. During mouse skin wound healing, the differentiated Gata6-lineage positive cells of the sebaceous duct are able to dedifferentiate. Here we have integrated lineage tracing and single-cell mRNA sequencing to uncover the underlying mechanism. Gata6-lineage positive and negative epidermal stem cells in wounds are transcriptionally indistinguishable. Furthermore, in contrast to reprogramming of induced pluripotent stem cells, the same genes are expressed in the epidermal dedifferentiation and differentiation trajectories, indicating that dedifferentiation does not involve adoption of a new cell state. We demonstrate that dedifferentiation is not only induced by wounding, but also by retinoic acid treatment or mechanical expansion of the epidermis. In all three cases, dedifferentiation is dependent on the master transcription factor c-Myc. Mechanotransduction and actin-cytoskeleton remodelling are key features of dedifferentiation. Our study elucidates the molecular basis of epidermal dedifferentiation, which may be generally applicable to adult tissues.

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Section: Methodsmentioning

confidence: 99%

Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation

Bernabé-Rubio,

Ali,

Bhosale

et al. 2023

Nat Cell Biol

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Strategies for visualizing inflammation

Zhang

Liu

Guo

et al. 2020

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As a basic innate immune response to the disordered tissue homeostasis, inflammation is related to the pathogenesis of multiple diseases, including bacterial infections, atherosclerosis, neurodegenerative diseases, and cancers. It is also a pivotal feature of some metabolic disorders such as diabetes and obesity. The visualization of in vivo inflammations can help us to comprehend the pathogenesis of these diseases and develop new solutions to diagnose them. Over the past few decades, a variety of strategies (eg, computed tomography, magnetic resonance imaging [MRI], and ultrasound [US] imaging) have been utilized for visualizing inflammations by imaging the structural changes of inflammatory tissues. Moreover, many recent studies have focused on some probes that can target or localize the inflammatory sites by specific binding to inflammation‐related molecules, being internalized by inflammatory cells, or becoming detectable only under inflammatory conditions. These probes can also be applied to visualize inflammations by MRI, positron emission tomography, single‐photon emission computed tomography, photoacoustic imaging, optical imaging (eg, fluorescence imaging, bioluminescence imaging, and chemiluminescence imaging), contrast‐enhanced US imaging, and the combined use of the abovementioned methods. This review not only summarizes the existing strategies for visualizing inflammations, but also discusses the limitations of the present strategies and the future directions on the development of new strategies for realizing the in vivo inflammation visualization.

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Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model

Martínez-Navarrete,

Guillot,

Lobita

et al. 2024

Drug Deliv. and Transl. Res.

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Several drugs can be used for treating inflammatory skin pathologies like dermatitis and psoriasis. However, for the management of chronic and long-term cases, topical administration is preferred over oral delivery since it prevents certain issues due to systemic side effects from occurring. Cyclosporin A (CsA) has been used for this purpose; however, its high molecular weight (1202 Da) restricts the diffusion through the skin structure. Here, we developed a nano-in-micro device combining lipid vesicles (LVs) and dissolving microneedle array patches (DMAPs) for targeted skin delivery. CsA-LVs allowed the effective incorporation of CsA in the hydrophilic DMAP matrix despite the hydrophobicity of the drug. Polymeric matrix composed of poly (vinyl alcohol) (5% w/v), poly (vinyl pyrrolidine) (15% w/v) and CsA-LV dispersion (10% v/v) led to the formation of CsA-LVs@DMAPs with adequate mechanical properties to penetrate the stratum corneum barrier. The safety and biocompatibility were ensured in an in vitro viability test using HaCaT keratinocytes and L929 fibroblast cell lines. Ex vivo permeability studies in a Franz-diffusion cell setup showed effective drug retention in the skin structure. Finally, CsA-LVs@DMAPs were challenged in an in vivo murine model of delayed-type hypersensitivity to corroborate their potential to ameliorate skin inflammatory conditions. Different findings like photon emission reduction in bioluminescence study, normalisation of histological damage and decrease of inflammatory cytokines point out the effectivity of CsA-LVs@DMAPs to treat these conditions. Overall, our study demonstrates that CsA-LVs@DMAPs can downregulate the skin inflammatory environment which paves the way for their clinical translation and their use as an alternative to corticosteroid-based therapies. Graphical Abstract

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Non-invasive bioluminescence imaging as a standardized assessment measure in mouse models of dermal inflammation

Abstract: For drug discovery and translational purposes, it is important that disease processes be tracked in vivo and possibly over a long period. We conclude that BLI is a valuable and reliable method for in-vivo measurement of dermal inflammation and potentially for inflammation resolution.

Cited by 5 publications

References 51 publications

Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation

Myc-dependent dedifferentiation of Gata6+ epidermal cells resembles reversal of terminal differentiation

Strategies for visualizing inflammation

Cyclosporin A-loaded dissolving microneedles for dermatitis therapy: Development, characterisation and efficacy in a delayed-type hypersensitivity in vivo model

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