COMPARATIVE PHOTOMICROGRAPHIC EXAMINATION OF INTEGUMENT FROM
EIGHT SPECIES OF MAMMALS INCLUDING TWO LINEAGES OF RESEARCH MINISWINE
Brown L. ¹, Kim D.Y. 3, Hanks C. ¹, Schnapp S. ¹, Brocksmith D.², White D. ¹, Stricker-Krongrad A.², Liu J.¹, Bouchard G.F.¹
¹Sinclair Research Center, LLC, Auxvasse, MO, USA; ²Sinclair BioResources, LLC, Auxvasse, MO, USA; 3Veterinary Medical Diagnostic Laboratory, University of Missouri, Columbia, MO, USA
ABSTRACT
Introduction: Skin is the largest organ in the body. Animals have skin which is generally similar
to human skin, however, species specific anatomical and biochemical differences exist. The integument of animal models may vary in skin surface topography, overall thickness and thickness
of specific layers, stratum corneum, epidermis, dermis density and collagen content, regional
blood flow, pelage (hair count), hair follicle size or density, and sub-dermal characteristics. Determination of which animal model most closely matches the skin of humans is important for
translational dermal research.
Objective/Rationale: Prepare magnified images of comparative skin histology and perform simple image analysis for differences or similarities.
Methods: Animal skin samples collected included Yucatan miniswine, Hanford miniswine, Cynomolgus monkey, Beagle dog, NZW rabbit, Hartley guinea pig, Sprague-Dawley rat, and CD-1
mouse. The human skin was acquired from a medical school. Samples were fixed in neutral
buffered formalin, processed, sectioned, stained with H&E, examined by microscope and photographed by veterinary dermatopathologist (DYK). The resulting skin images generated by Olympus MicroSuiteTM were compared side-by-side at equivalent magnification.
Results: Visual comparison of images suggest the skin of swine and human look the most similar while the skin of rodents (rat, mouse) has a much thinner epidermis. The skin of rabbit and
guinea pig appear to consist predominantly of hair shafts/hair follicles combined with thin epidermis. Monkey and dog skin were next most similar to the human skin.
Species
Species
Human
Miniswine
Miniswine
Gender
Caucasian
Not
Recorded
Standard
Yucatan
Male
Hanford
Age
Hair
Density
INTRODUCTION
Skin is the largest organ in the body. Animals have skin which is generally similar to human skin,
however, species specific anatomical and biochemical differences exist. The integument of animal models may vary in skin surface topography, overall thickness and thickness of specific
layers, stratum corneum, epidermis, dermis density and collagen content, regional blood flow,
pelage (hair), hair follicle density, and sub-dermis characteristics. Hairless or nude animals have
empty hair follicles but the density may be reduced from the haired counterpart. Hair follicles
are important to drug absorption for certain drug classes. Determination of which animal model
most closely matches the skin of humans is important for translational dermal research.
Objective/Rationale: Prepare magnified images of comparative skin histology and perform
quick image analysis by the human eye.
Methods: Animal skin samples were collected humanely from research animals either at necropsy, termination or in surgery under anesthesia. Included were Yucatan miniswine, Hanford
miniswine, Cynomolgus monkey, Beagle dog, NZW rabbit, Hartley guinea pig, Sprague-Dawley
rat, and CD-1 mouse (Table 1). Human skin images were obtained from a medical school.
Hair
Color
Integument
Color
Skin Site
Sampled
5 yrs
Thin
‘Hairless’
Young
Adult
Well Haired
Pelage
White
Grey
Slate Grey
Lumbar
Back
White
Lumbar
Back
Monkey
(NHP)
Cynomolgus
Male
4.3 yrs
Thin
Brown
White
Shoulder
Dog
Beagle
Female
6 yrs
Well
Haired
Tri
White
Lumbar
Back
Well
Haired
White
Rabbit
NZW
Guinea Pig
Hartley
Albino Rat
SpragueDawley
Albino Mouse
CD-1
Male
3.5
Months
Formalin
Fixation
H&E
Stain
Upper
Back
Adult
Female
2.5
Months
Well
Haired
Female
3
Months
Well
Haired
Male
2
Months
Well
Haired
White
White
White
White
Lumbar
Back
Primary Hair
(PH)
Secondary
Hair (SH)
Sebaceous
Gland (S)
Apocrine
Gland (A)1
Eccrine
Gland (E)
Miniswine,
Yucatan
Miniswine,
Hanford
Monkey
(NHP), Cyno
Dog, Beagle
Rabbit, NZW
Guinea Pig,
Hartley
Albino Rat,
S-D
Albino Mouse,
CD-1
The human skin sample was acquired from the local University School of Medicine following
established protocols and informed consent. Samples were fixed in neutral buffered formalin,
processed, sectioned, stained with H&E, examined by microscope and photographed by professional dermatopathologist (DYK). The resulting skin jpeg images (Figures 1-9) generated by
Olympus MicroSuiteTM were compared side-by-side at equivalent magnification.
Results: The results suggest the adherent skin of swine and human look the most similar. The
loose skin of rodents (rat, mouse) has a much thinner epidermis. The skin of rabbit and guinea
pig appear to consist predominantly of hair shafts combined with thin epidermis. Table 2 lists
the image legends for each species.
Increasingly the scientific community has recognized the similar anatomy and physiology between swine and humans, with the swine dermal system being very comparable to humans
with regards to the anatomical, physiological, metabolic, and histological features. Other organs
and systems (cardiovascular, digestive, renal) are also analogous to human systems. Thus, the
absorption, distribution, metabolism, and elimination of drugs in swine are generally very predictive of human metabolism, distribution, pharmaco/toxicokinetics. This has led to an increase
in the use of miniature swine in preclinical research, including dermal toxicology and DMPK,
and recognition by regulatory authorities that swine are an appropriate animal model for these
evaluations. Animal model skin similarities and differences have been previously reported (Banga 2011, Zhai et al., 2008, Riviere 2008, Swindle 2008, Monterio-Riviere 1991 & 1996). Skin
histological variations by species are easily identified when magnified sufficiently to allow visualization of layers, pelage and adnexa. Among the many factors which are known to affect percutaneous drug uptake are the thickness of stratum corneum, hair follicle density for certain
classes of drugs, biochemical makeup of the epidermal mortar (brick & mortar concept), skin
regional blood flow, and polar vs. nonpolar drug absorption characteristics. Some species (human, swine, NHP) have skin which is adherent to underlying structures while others have thin
non-adherent or ‘loose’ skin (rat, mouse, rabbit, guinea pig, hamster). Swine are known to be
good models for human dermal pharmacology, dermal toxicology and skin wound healing/burn
studies. Selection of dermal testing models for best human translational research requires an
understanding of the skin surface topography, microanatomy, pelage density, hair follicle density, skin glands or adnexa, biochemistry, physiology, and genetics. Although the sample size/species is small for this histological study, this abbreviated study still gives a general understanding
of comparative dermal anatomy and histology.
CONCLUSION
The swine (Yucatan & Hanford) skin images reported herein are visually most like the human
skin image from a microanatomy perspective.
REFERENCES
1.Banga AK (2011). Ch 1 Percutaneous Absorption and Enhancement Strategies, and Ch 2 Experimental Methods and Tools for Transdermal Delivery by Physical Enhancement Methods
In: Transdermal and Intradermal Delivery of Therapeutic Agents, CRC Press: Boca Raton, p126, p27-51.
2.Zhai H, Wilhelm KP, Maibach HI (Eds). Marzulli & Maibach’s Dermatotoxicology. Informa Health Care, 7th Ed, 2008.
3.Riviere JE (2008). Comparative Aspects of Topical Delivery. Powerpoint Presented at Skin Forum EU Meeting, (CCTRP) June 2008. http://www.skin-forum.eu/presentations/Riviere%2
Skin%20Forum%20June%2008.pdf
4.Swindle MM, DVM (2008). Sinclair Technical Bulletin, Porcine Integumentary System Model-Part1.pdf.http://www.sinclairbioresources.com/Downloads/TechnicalBulletins/Porcine%20Integumentary%20System%20Model-Part%201.pdf
White
Lumbar
Back
5.Monteiro-Riviere NA, and J Riviere (1996). The pig as a model for cutaneous pharmacology and toxicology research. In Tumbleson ME, Schook LB (Eds). Advances in Swine in Biomedical
Research, Vol 2. New York: Plenum Press, 425-458.
White
Lumbar
Back
6.Monteiro-Riviere NA (1991). Comparative Anatomy, Physiology, and Biochemistry
of Mammalian Skin. In: Dermal and Ocular Toxicology: Fundamentals and Methods
DW Hobson). CRC Press, Inc., New York, New York, Chapter 1, 3-71.
White
Lumbar
Back
7.Monteiro-Riviere NA, Bristol DG, Manning TO, and Riviere JE (1990).
Interspecies and interregional analysis of the comparative
histological thickness and laser Doppler blood flow
measurements at five cutaneous sites in nine
species, J. Invest. Dermatol. 95: 582-586.
Skin samples taken from the dorsum or lumbar back, or other designated site of normal animals. Samples were elliptical scalpel incisions for fixation and preparation of histology. Samples (3-4 mm wide by 1.5-2 cm long, deep to adipose) were fixed in 10% NBF in labeled specimen jars. Thick fixation cassettes with cardboard inserts were used to keep the skin from curling. 40X H&E jpeg color lateral profile images were obtained showing the stratum corneum, epidermis and the dermis.
1
Hair Follicle
(H)
Human
TABLE 1: CHARACTERISTICS OF SKIN SAMPLES USED IN STUDY
Genetic
Group
DISCUSSION
TABLE 2: IMAGE LEGENDS
Conclusion(s): The swine (Yucatan & Hanford) skin images are visually most like those of the
human images.
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