ArticleTissue engineering. Part A2015
Development of a Full-Thickness Human Skin Equivalent In Vitro Model Derived from TERT-Immortalized Keratinocytes and Fibroblasts.
Article in Tissue engineering. Part A, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed.
- Vascularized human skin assembloids model compartmental skin organization and immune responsiveness in vitro.Experimental & molecular medicine · 2026Article
- IFN-κ directs antiviral immunity in human skin.bioRxiv : the preprint server for biology · 2026Article
- Method and Analysis of High-Calcium Induced Differentiation of Human Primary KeratinocytesMethods and protocols · 2026Article
- Engineering in vitro models to replicate the complexity of chronic wounds.Nature communications · 2026Review
- Optical, Tomographic, and Mass Spectrometry Imaging Methods for Burn Wounds: Capabilities, Limitations, and Clinical Potential.Biomedicines · 2026Review
- A Novel Microfluidic System for 3D Epidermis and Full-Thickness Skin Growth for Nanoparticle Safety Assessment.Advanced healthcare materials · 2026Article
- Combining advanced 3D spheroid-based skin models with deep-learning-based image analysis enables in-depth investigation of keratinocyte differentiation and barrier function.Frontiers in bioengineering and biotechnology · 2026Article
- Establishment of immortalized human minor salivary gland cells and chemokine expression induced by IFN-γ, TNF-α, and IL-1β.Odontology · 2025Article
- A hair-follicle reconstructed in vitro immunocompetent skin model for prediction of the sensitizing potential of chemicals.Archives of toxicology · 2025Article
- Development of Human Skin Equivalents with Inducible Ceramide Depletion for In Vitro Modeling of Lipid Impairment.JID innovations : skin science from molecules to population health · 2025Article
- Evaluating blue light impact on reconstructed human epidermis using laser speckle imaging.Journal of biomedical optics · 2025Article
- Development and characterization of a novel immortalized human vaginal fibroblast cell line for advanced applications in reproductive health.Reproductive biology and endocrinology : RB&E · 2025Article
- Do Melanocytes Have a Role in Controlling Epidermal Bacterial Colonisation and the Skin Microbiome?Experimental dermatology · 2025Article
- SenPred: a single-cell RNA sequencing-based machine learning pipeline to classify deeply senescent dermal fibroblast cells for the detection of an in vivo senescent cell burden.Genome medicine · 2025Article
- Article
- Effects of Th1/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes.Frontiers in physiology · 2025Article
- Engineering a Pigmented Skin Equivalent That Is Responsive to External Stimuli.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Diversity of human skin three-dimensional organotypic cultures.Current opinion in genetics & development · 2024Review
- Liposomes and Their Therapeutic Applications in Enhancing Psoriasis and Breast Cancer Treatments.Nanomaterials (Basel, Switzerland) · 2024Review
- Dual-mode OCT/fluorescence system for monitoring the morphology and metabolism of laser-printed 3D full-thickness skin equivalents.Biomedical optics express · 2024Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, human skin equivalents (HSEs) used for in vitro assays (e.g., for wound healing) make use of primary human skin cells. Limitations of primary keratinocytes and fibroblasts include availability of donor skin and donor variation. The use of physiologically relevant cell lines could solve these limitations. The aim was to develop a fully differentiated HSE constructed entirely from human skin cell lines, which could be applied for in vitro wound-healing assays. Skin equivalents were constructed from human TERT-immortalized keratinocytes and fibroblasts (TERT-HSE) and compared with native skin and primary HSEs. HSEs were characterized by hematoxylin-eosin and immunohistochemical stainings with markers for epidermal proliferation and differentiation, basement membrane (BM), fibroblasts, and the extracellular matrix (ECM). Ultrastructure was determined with electron microscopy. To test the functionality of the TERT-HSE, burn and cold injuries were applied, followed by immunohistochemical stainings, measurement of reepithelialization, and determination of secreted wound-healing mediators. The TERT-HSE was composed of a fully differentiated epidermis and a fibroblast-populated dermis comparable to native skin and primary HSE. The epidermis consisted of proliferating keratinocytes within the basal layer, followed by multiple spinous layers, a granular layer, and cornified layers. Within the TERT-HSE, the membrane junctions such as corneosomes, desmosomes, and hemidesmosomes were well developed as shown by ultrastructure pictures. Furthermore, the BM consisted of a lamina lucida and lamina densa comparable to native skin. The dermal matrix of the TERT-HSE was more similar to native skin than the primary construct, since collagen III, an ECM marker, was present in TERT-HSEs and absent in primary HSEs. After wounding, the TERT-HSE was able to reepithelialize and secrete inflammatory wound-healing mediators. In conclusion, the novel TERT-HSE, constructed entirely from human cell lines, provides an excellent opportunity to study in vitro skin biology and can also be used for drug targeting and testing new therapeutics, and ultimately, for incorporating into skin-on-a chip in the future.
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