Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing

Yap, Wei Hsum and Cheah, Toh Yang and Yong, Leng Chuan and Chowdhury, Shiplu Roy and Ng, Min Hwei and Kwan, Zhenli and Kong, Chee Kwan and Goh, Bey-Hing (2021) Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing. Journal of Biosciences, 46 (3). ISSN 0250-5991, DOI

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Psoriasis is a chronic skin disease characterized by thickening and disorganization of the skin's protective barrier. Although current models replicate some aspects of the disease, development of therapeutic strategies have been hindered by absence of more relevant models. This study aimed to develop and characterize an in vitro psoriatic human skin equivalent (HSE) using human keratinocytes HaCat cell line grown on fibroblasts-derived matrices (FDM). The constructed HSEs were treated with cytokines (IL-1 alpha, TNF-alpha, IL-6, and IL-22) to allow controlled induction of psoriasis-associated features. Histological stainings showed that FDM-HSE composed of a fully differentiated epidermis and fibroblast-populated dermis comparable to native skin and rat tail collagen-HSE. Hyperproliferation (CK16 and Ki67) and inflammatory markers (TNF-alpha and IL-6) expression were significantly enhanced in the cytokine-induced FDM- and rat tail collagen HSEs compared to non-treated HSE counterparts. The characteristics were in line with those observed in psoriasis punch biopsies. Treatment with all-trans retinoic acid (ATRA) has shown to suppress these effects, where HSE models treated with both ATRA and cytokines exhibit histological characteristics, hyperproliferation and differentiation markers expression like non-treated control HSEs. Cytokine-induced FDM-HSE, constructed entirely from human cell lines, provides an excellent opportunity for psoriasis research and testing new therapeutics.

Item Type: Article
Funders: Taylor's Research Grant Scheme Major Grant [TRGS/MFS/1/2015/SBS/013]
Uncontrolled Keywords: Fibroblasts-derived matrices; psoriasis; in vitro model; human skin equivalent
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Medicine > Medicine Department
Depositing User: Ms Zaharah Ramly
Date Deposited: 01 Jul 2022 07:25
Last Modified: 01 Jul 2022 07:25

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