ArticlePloS one2013
Keratinocytes propagated in serum-free, feeder-free culture conditions fail to form stratified epidermis in a reconstituted skin model.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 70 citations in OpenAlex.
- Cellularized Skin Substitute Bioengineering for Regenerative Medicine: Cell Sources, Culture Strategies, and Transition Toward Defined, Xeno-Free Culture Systems.Advanced healthcare materials · 2026Review
- From basic biology to engineered therapies: the keratinocyte stem cell playbook.Frontiers in medical technology · 2026Review
- Effects of Th1/Th17 and Th2 cytokines on lipid metabolism in differentiated keratinocytes.Frontiers in physiology · 2025Article
- Production of Tissue-Engineered Skin Substitutes for Clinical Applications: Elimination of Serum.International journal of molecular sciences · 2023Article
- The use of human-derived feeder layers for the cultivation of transplantable human epidermal cell sheet to repair second degree burn wounds.Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) · 2023Article
- A Newly Developed Chemically Defined Serum-Free Medium Suitable for Human Primary Keratinocyte Culture and Tissue Engineering Applications.International journal of molecular sciences · 2023Article
- Developing a bioink for single-step deposition and maturation of human epidermis.International journal of bioprinting · 2023Article
- Injectable and biofunctionalized fibrin hydrogels co-embedded with stem cells induce hair follicle genesis.Regenerative biomaterials · 2023Article
- Adaptive multi-degree-of-freedom in situ bioprinting robot for hair-follicle-inclusive skin repair: A preliminary study conducted in mice.Bioengineering & translational medicine · 2022Article
- Evaluation of native and non-native biomaterials for engineering human skin tissue.Bioengineering & translational medicine · 2022Article
- Optimizing large-scale autologous human keratinocyte sheets for major burns-Toward an animal-free production and a more accessible clinical application.Health science reports · 2022Article
- Article
- Paclitaxel-Induced Epidermal Alterations: An In Vitro Preclinical Assessment in Primary Keratinocytes and in a 3D Epidermis Model.International journal of molecular sciences · 2022Article
- Differential Marker Expression between Keratinocyte Stem Cells and Their Progeny Generated from a Single Colony.International journal of molecular sciences · 2021Article
- Cells/colony motion of oral keratinocytes determined by non-invasive and quantitative measurement using optical flow predicts epithelial regenerative capacity.Scientific reports · 2021Article
- Bioengineered Skin Intended as In Vitro Model for Pharmacosmetics, Skin Disease Study and Environmental Skin Impact Analysis.Biomedicines · 2020Review
- Chemically defined and xenogeneic-free culture method for human epidermal keratinocytes on laminin-based matrices.Nature protocols · 2020Article
- In Vitro Expansion of Keratinocytes on Human Dermal Fibroblast-Derived Matrix Retains Their Stem-Like Characteristics.Scientific reports · 2019Article
- Rutile nano-bio-interactions mediate dissimilar intracellular destiny in human skin cells.Nanoscale advances · 2019Article
- Serum affects keratinization and tight junctions in three-dimensional cultures of the mouse keratinocyte cell line COCA through retinoic acid receptor-mediated signaling.Histochemistry and cell biology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Primary human epidermal stem cells isolated from skin tissues and subsequently expanded in tissue culture are used for human therapeutic use to reconstitute skin on patients and to generate artificial skin in culture for academic and commercial research. Classically, epidermal cells, known as keratinocytes, required fibroblast feeder support and serum-containing media for serial propagation. In alignment with global efforts to remove potential animal contaminants, many serum-free, feeder-free culture methods have been developed that support derivation and growth of these cells in 2-dimensional culture. Here we show that keratinocytes grown continually in serum-free and feeder-free conditions were unable to form into a stratified, mature epidermis in a skin equivalent model. This is not due to loss of cell potential as keratinocytes propagated in serum-free, feeder-free conditions retain their ability to form stratified epidermis when re-introduced to classic serum-containing media. Extracellular calcium supplementation failed to improve epidermis development. In contrast, the addition of serum to commercial, growth media developed for serum-free expansion of keratinocytes facilitated 3-dimensional stratification in our skin equivalent model. Moreover, the addition of heat-inactivated serum improved the epidermis structure and thickness, suggesting that serum contains factors that both aid and inhibit stratification.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.