The development of alternative approaches for safety and efficacy testing that avoid the use of animals is a worldwide trend, which relies on the improvement of current models and tools so that they better reproduce human biology. Human skin from elective plastic surgery is a promising experimental model to test the effects of topically applied products. As the structure of native skin is maintained, including cell population (keratinocytes, melanocytes, Langerhans cells and fibroblasts) and dermal matrix (containing collagen, elastin, glycosaminoglycans, etc.), it most closely matches the effects of substances on in vivo human skin. In this review, we present a collection of results that our group has generated over the last years, involving the use of human skin and scalp explants, demonstrating the feasibility of this model. The development of a test system with ex vivo skin explants, of standard size and thickness, and cultured at the air–liquid interface, can provide an important tool for understanding the mechanisms involved in several cutaneous disorders.
RussellWMSBurchRL. The principles of humane experimental technique. London: Methuen, 1959, 238 pp.
2.
RandallMJJüngelARimannM, et al.Advances in the biofabrication of 3D skin in vitro: healthy and pathological models. Front Bioeng Biotechnol2018; 6: 154.
3.
FentemJHBriggsDChesnéC, et al.A prevalidation study on in vitro tests for acute skin irritation, results and evaluation by the management team. Toxicol in Vitro2001; 15: 57–93.
4.
PortesPGrandidierM-HCohenC, et al.Refinement of the EPISKIN protocol for the assessment of acute skin irritation of chemicals: follow-up to the ECVAM prevalidation study. Toxicol in Vitro2002; 16: 765–770.
5.
KandárováHLiebschMGenschowE, et al.Optimisation of the EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests. ALTEX2004; 21: 107–114.
6.
KandárováHLiebschMGernerI, et al.The EpiDerm test protocol for the upcoming ECVAM validation study on in vitro skin irritation tests — an assessment of the performance of the optimised test. Altern Lab Anim2005; 33: 351–367.
7.
CotovioJGrandidierM-HPortesP, et al.The in vitro acute skin irritation of chemicals: optimisation of the EPISKIN prediction model within the framework of the ECVAM validation process. Altern Lab Anim2005; 33: 329–349.
8.
SpielmannHHoffmannSLiebschM, et al.The ECVAM international validation study on in vitro tests for acute skin irritation: report on the validity of the EPISKIN and EpiDerm assays and on the skin integrity function test. Altern Lab Anim2007; 35: 559–601.
9.
EskesCColeTHoffmannS, et al.The ECVAM international validation study on in vitro tests for acute skin irritation: selection of test chemicals. Altern Lab Anim2007; 35: 603–619.
10.
CotovioJGrandidierM-HLelièvreD, et al.In vitro acute skin irritancy of chemicals using the validated EPISKIN model in a tiered strategy — results and performances with 184 cosmetic ingredients. AATEX2007; 14: 351–358.
11.
KatohMHamajimaFOgasawaraT, et al.Assessment of human epidermal model LabCyte EPI-MODEL for in vitro skin irritation testing according to European Centre for the Validation of Alternative Methods (ECVAM)-validated protocol. J Toxicol Sci2009; 34, 327–334.
12.
KatohMHataK. Refinement of LabCyte EPI-MODEL24 skin irritation test method for adaptation to the requirements of OECD Test Guideline 439. AATEX2011; 16: 111–122.
13.
KojimaHAndoYIdeharaK, et al.Validation study of the in vitro skin irritation test with the LabCyte EPI-MODEL24. Altern Lab Anim2012; 40: 33–50.
14.
FacchiniGEberlinSClericiSP, et al.Ultraviolet A photosensitivity profile of dexchlorpheniramine maleate and promethazine-based creams: anti-inflammatory, antihistaminic, and skin barrier protection properties. J Cosmet Dermatol2017; 16: e59–e67.
15.
EberlinSFacchiniGEberlinS, et al.Alternative methodology for the study of infrared-A radiation effects on human skin. Surg Cosmet Dermatol2016; 8: 115–120.
16.
AyresELCostaAEberlinS, et al.Ex vivo study for evaluating the whitening activity of Pycnogenol® after exposure to ultraviolet and infrared radiations, and visible light. Surg Cosmet Dermatol2015; 7: 303–307.
17.
NakamuraMRikimaruTYanoT, et al.Full-thickness human skin explants for testing the toxicity of topically applied chemicals. J Invest Dermatol1990; 95: 325–332.
18.
SandtJRoguetRCohenC, et al.The use of human keratinocytes and human skin models for predicting skin irritation. Altern Lab Anim1999; 27: 723–743.
19.
VaraniJPeronePSpahlingerDM, et al.Human skin in organ culture and human skin cells (keratinocytes and fibroblasts) in monolayer culture for assessment of chemically induced skin damage. Toxicol Pathol2007; 35: 693–701.
20.
MessagerSHannACGoddardPA, et al.Assessment of skin viability: is it necessary to use different methodologies?Skin Res Technol2003; 9: 321–330.
21.
MalininTIPerryVP. A review of tissue organ and viability assay. Cryobiol1967; 4: 104–115.
22.
KazemSLinssenECGibbsS. Skin metabolism phase I and phase II enzymes in native and reconstructed human skin: a short review. Drug Discov Today2019; 24: 1899–1910.
23.
FinchPWRubinJSMikiT, et al.Human KGF is FGF-related with properties of a paracrine effector of epithelial cell growth. Science1989; 245: 752–755.
24.
HiraiYTakebeKTakashinaM, et al.Epimorphin: a mesenchymal protein essential for epithelial morphogenesis. Cell1992; 69: 471–481.
25.
NishiyamaTTsunenagaMAkutsuN, et al.Role of dermal–epidermal communication on regulation of skin structure and function. In: TagamiHParrishJAOzawaT (ed) Skin: interface of a living system. Amsterdam: Elsevier BV, 1998, pp. 119–137.
26.
NishiyamaTAmanoSBurgesonRE. Structure and molecular assembly of the dermal-epidermal attachment complex in skin. Connective Tissue1998; 30: 213–217.
27.
GilbertPMWeaverVM. Cellular adaptation to biomechanical stress across length scales in tissue homeostasis and disease. Semin Cell Dev Biol2017; 67: 141–152.
ChengWYan-huaRFang-gangN, et al.The content and ratio of type I and III collagen in skin differ with age and injury. African J Biotechnol2011; 10: 2524–2529.
30.
RiitaRMataleenaPArjaJ. Increased expression of collagen type and in human skin as a consequence of radiotherapy. Arch Dermatol Res2002; 294: 178–184.
31.
GarreANardaMValderas-MartinezP, et al.Antiaging effects of a novel facial serum containing l-ascorbic acid, proteoglycans, and proteoglycan-stimulating tripeptide: ex vivo skin explant studies and in vivo clinical studies in women. Clin Cosmet Invest Dermatol2018; 11: 253–263.
32.
BogdanowiczPHaureMJCerutiI, et al.Results from in vitro and ex vivo skin aging models assessing the antiglycation and anti-elastase MMP-12 potential of glycylglycine oleamide. Clin Cosmet Investig Dermatol2016; 9: 143–150.
33.
SondenheimerKKrutmannJ. Novel means for photoprotection. Front Med2018; 5: 162.
34.
FacchiniGda SilvaMSPinheiroALTA, et al.Transcriptome (RNA-Seq) analysis of human skin exposed to infrared-A radiation: new targets for photodamage. IFSCC Mag2019; 22: 101–108.
35.
KrakowskiACEichenfieldLFDohilMA. Management of atopic dermatitis in the pediatric population. Pediatrics2008; 122: 812–824.
36.
McKennaSPDowardLC. Quality of life of children with atopic dermatitis and their families. Curr Opin Allergy Clin Immunol2008; 8: 228–231.
37.
AkdisCAAkdisMBieberT, et al.Diagnosis and treatment of atopic dermatitis in children and adults: European academy of allergology and clinical immunology/American academy of allergy, asthma and immunology/PRACTALL consensus report. J Allergy Clin Immunol2006; 118: 152–169.
38.
ImokawaGAbeAJinK, et al.Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?J Invest Dermatol1991; 96: 523–526.
39.
MelnikBHollmannJPlewigG. Decreased stratum corneum ceramides in atopic individuals — a pathobiochemical factor in xerosis?Br J Dermatol1988; 119: 547–549.
40.
MacheleidtOKaiserHWSandhoffK. Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol2002; 119: 166–173.
41.
Di NardoAWertzPGiannettiA, et al.Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol1998; 78: 27–30.
42.
MelnikBHollmannJHofmannU, et al.Lipid composition of outer stratum corneum and nails in atopic and control subjects. Arch Dermatol Res1990; 282: 549–551.
43.
YamamotoASerizawaSItoM, et al.Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res1991; 283: 219–223.
44.
SeguchiTCuiCYKusudaS, et al.Decreased expression of filaggrin in atopic skin. Arch Dermatol Res1996; 288: 442–446.
45.
JensenJMFolster-HolstRBaranowskyA, et al.Impaired sphingomyelinase activity and epidermal differentiation in atopic dermatitis. J Invest Dermatol2004; 122: 1423–1431.
46.
KimBELeungDYBoguniewiczM, et al.Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol2008; 126: 332–337.
47.
YamamotoMHarunaTYasuiK, et al.A novel atopic dermatitis model induced by topical application with Dermatophagoides farinae extract in NC/Nga mice. Allergol Int2007; 56: 139–148.
48.
OECD. Test No. 428: Skin Absorption: In Vitro Method, OECD Guidelines for Testing of Chemicals. Paris: Organisation for Economic Cooperation and Development, 2004, 8 pp.
49.
MackieDMJahnkeJPBenyaminMS, et al.Simple, fast, and accurate methodology for quantitative analysis using Fourier transform infrared spectroscopy, with bio-hybrid fuel cell examples. MethodsX2016; 21: 128–138.
50.
CharltonNPMurphyLTParker CoteJL, et al.The toxicity of picaridin containing insect repellent reported to the national poison data system. Clin Toxicol2016; 54: 655–658.
51.
JacobiUWeigmannHJUlrichJ, et al.Estimation of the relative stratum corneum amount removed by tape stripping. Skin Res Technol2005; 11: 91–96.
52.
TruebR. Oxidative stress in ageing of hair. Int J Trichol2009; 1: 6–14.
53.
LiuCSKaoSHWeiYH. Smoking-associated mitochondrial DNA mutations in human hair follicles. Environ Mol Mutagen1997; 30: 47–55.
54.
DallobALSadickNSUngerW, et al.The effect of finasteride, a 5 alpha-reductase inhibitor, on scalp skin testosterone and dihydrotestosterone concentrations in patients with male pattern baldness. J Clin Endocrinol Metab1994; 79: 703–706.
55.
FuchsE. The tortoise and the hair: slow-cycling cells in the stem cell race. Cell2009; 137: 811–819.
