# Long-Term Human Skin Platform for Modeling Chronic Inflammation, Environmental Stress, and Therapeutic Intervention

Article · Sharma PK, Schaafsma E, Anderson E, Chiari J, Thompson P, Galt E, Lee S, Holsapple J, Hein S, Coates BL, Michaud J, Zuccaro S, Kent L, Hinojosa C, Jang KJ

- Archive id: doi:10.1002/advs.78035
- Published: 2026-09-29
- Venue: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
- DOI: https://doi.org/10.1002/advs.78035
- PMID: 42811603
- PMCID: PMC13624414
- Citations: 0
- Source URL: https://doi.org/10.1002/advs.78035
- PDF: https://europepmc.org/articles/PMC13624414/pdf
- Provenance: europepmc

## Abstract

Chronic inflammation drives tissue dysfunction and aging, yet the dynamic interplay between persistent inflammatory signaling and structural deterioration remains difficult to study in human-relevant systems. Here, an advanced long-term human skin platform is presented that preserves native tissue architecture and epidermal, stromal, and immune-associated molecular programs for up to 4 weeks. Time-course RNA sequencing of 199 tissue samples from 20 donors revealed an early culture adaptation phase followed by stabilization of tissue-associated transcriptional programs. Using this system, sustained IL-17/IL-22 stimulation over 3 weeks induced chronic inflammatory transcriptional programs, progressive histopathological changes, and persistent secretion of IL-8, MCP-1, S100A8/A9, and MMP-1, which was broadly suppressed by the Janus kinase inhibitor tofacitinib. In aged donor tissue, prolonged senolytic-associated treatment attenuated inflammatory and remodeling pathways and reduced senescence-associated secretory factors, including IL-6 and MMP-1, with significant treatment-associated effects evident at Week 3 but not Week 1. Finally, ultraviolet B exposure triggered coordinated stress and inflammatory responses that were mitigated using topical sunscreen, demonstrating compatibility with environmental stress modeling and topical intervention. Together, these findings establish a versatile human skin platform for modeling chronic inflammation, aging-associated tissue remodeling, and environmental stress, providing a translational framework for investigating skin tissue dysfunction and evaluating therapeutic interventions.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Biology of Aging & Longevity](https://space-kitty.com/topics/aging-longevity)

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