Hamster Flank Organ Acne Model / Overview


Introduction

Hamster flank organ acne model is an animal model which has been extensively used for the study of compounds inhibiting the response of sebaceous glands to hormones, anti-androgens, and retinoids.

The hamster flank organ is composed of clusters of large sebaceous glands.

This organ has a bilateral localization on animals abdomen and is used to produce pheromones and marking molecules of mature males.

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Protocol summary

Acne preclinical models

Hamster mature males with application of compounds / new drugs on flank organ on each side

Histology evaluation flank organ size and sebaceous glands

Evaluation of in vivo / ex vivo / analysis secondary efficacy  endpoints

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Typical results

Typical results obtained with this model are presented below:

EvaluationParameterGroup control
(excipient / topical)
Test group
(retinoid / topical)
In vivoBodyweightNE (No Effect)NE or decrease
Flank organ sizeNESlight decrease
Back skin scaling
(visual scoring)
NESlight increase (dry skin appearance)
Back skin erythema
(visual scoring)
NEIncrease (irritation)
Back skin thickness
(calipering)
NENE or increase
Epidermis thickness
(OCT / Optical Coherence Tomography)
NEIncrease
Ex vivo
(histology)
Sebaceous glandsNEDecrease
Sebum surfaceNEDecrease
Sebaceous glands inter-lobular spacesNEIncrease
Epidermis thicknessNEIncrease
(epidermal hyperplasia)
Dermis inflammationNEIncrease
(local inflammation slight to moderate)

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Hamster Flank Organ Acne Model / Detailed protocol


Hamster / Syrian gold strain

– >10 weeks old / Male with SPF status

– Randomization on bodyweight & organs sizes

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Application of dermatological pharmaceutical products

– Ready to use formulations / Formulation screening on request

Topical & Oral routes / Reference drugs: Isotretinoin or Adapalene or Bexarotene

Intra-dermal route (i.e. Medical Devices or injectable drugs)

– Treatment duration: >3 weeks

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Evaluation of clinical macroscopic signs

– Body weight / General behavior

– Flank organ size and length / Caliper

– Back skin thickness / Caliper

– Flank organ and surrounding skin macroscopic description:

Scaling (skin dryness)

Erythema (skin redness)

Other macroscopic skin observations

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In vivo imaging

– Macroscopical observation: Digital pictures of flank organs

– Sub-macroscopical exploration: Optical Coherence Tomography (OCT) for epidermis thickness measurement and superior sebaceous gland structure (on development)

– Ultrasonography for flank organ size evaluation

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Ex vivo imaging

– Histology on back skin slices obtained from paraffin blocks or frozen blocks

– HES (Hemalun-Eosin-Safran) / Overall evaluation of efficacy (sebaceous glands surface / sebum surface)

– Immuno-histochemistry

Ki67 staining for keratinocyte / fibroblast / sebocyte proliferation index calculation

Other stainings on request

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Other ex vivo imaging techniques of interest:

  3D reconstruction of sebaceous glands for volume evaluation

  Light Sheet microscopy (in collaboration)

  MALDI imaging (in collaboration)

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Hamster Flank Organ Acne model / Conclusion


Hamster flank organ model is a first intention model validated with retinoids and anti-androgens family of compounds.

6 animals per group are generally sufficient to underline anti-acne effect of new therapeutics (based on difference of at least 20% / sebaceous glands surface or sebum surface).

Cautions to be taken on this model :

Use of previously untested excipients should be avoid as they could cause false positive, false negative or local irritation

Formulation physico-chemistry must be well known (pH, osmolarity, etc…)

Drug pharmacokinetics / ADME / transcutaneous passage should be known to optimize dosing

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CIR _ Research Tax Credit Imavita

Do not hesitate to contact us if you need more information or a quotation on this model.

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Bibliography of interest

  1. Franz, T. J., et al. The hamster flank organ model: is it relevant to man? J. Invest. Dermatol. 93, 475–9 (1989).
  2. Weissmann, A., et al. Morphometric Studies of the Hamster Flank Organ: An Improved Model to Evaluate Pharmacologic Effects on Sebaceous Glands. J. Invest. Dermatol. 82, 522–525 (1984).
  3. Gomez, E. C. & Moskowitz, R. J. Effect of 13-cis-retinoic acid on the hamster flank organ. J. Invest. Dermatol. 74, 392–397 (1980).
  4. Orentreich, N. et al. The local antiandrogenic effect of the intracutaneous injection of progesterone in the flank organ of sexually mature male Syrian golden hamster. Arch. Dermatol. Res. 276, 401–405 (1984).
  5. Piskin, S. & Uzunali, E. A review of the use of adapalene for the treatment of acne vulgaris. Ther. Clin. Risk Manag. 3, 621–624 (2007).

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