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

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 d...

Full description

Saved in:
Bibliographic Details
Main Authors: Yap, Wei Hsum, Cheah, Toh Yang, Yong, Leng Chuan, Chowdhury, Shiplu Roy, Ng, Min Hwei, Kwan, Zhenli, Kong, Chee Kwan, Goh, Bey-Hing
Format: Article
Published: Indian Academy of Sciences 2021
Subjects:
Online Access:http://eprints.um.edu.my/33999/
Tags: Add Tag
No Tags, Be the first to tag this record!
id my.um.eprints.33999
record_format eprints
spelling my.um.eprints.339992022-07-01T07:25:32Z http://eprints.um.edu.my/33999/ Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing Yap, Wei Hsum Cheah, Toh Yang Yong, Leng Chuan Chowdhury, Shiplu Roy Ng, Min Hwei Kwan, Zhenli Kong, Chee Kwan Goh, Bey-Hing QH301 Biology 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. Indian Academy of Sciences 2021-09 Article PeerReviewed 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 https://doi.org/10.1007/s12038-021-00205-y <https://doi.org/10.1007/s12038-021-00205-y>. 10.1007/s12038-021-00205-y
institution Universiti Malaya
building UM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Malaya
content_source UM Research Repository
url_provider http://eprints.um.edu.my/
topic QH301 Biology
spellingShingle QH301 Biology
Yap, Wei Hsum
Cheah, Toh Yang
Yong, Leng Chuan
Chowdhury, Shiplu Roy
Ng, Min Hwei
Kwan, Zhenli
Kong, Chee Kwan
Goh, Bey-Hing
Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
description 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.
format Article
author Yap, Wei Hsum
Cheah, Toh Yang
Yong, Leng Chuan
Chowdhury, Shiplu Roy
Ng, Min Hwei
Kwan, Zhenli
Kong, Chee Kwan
Goh, Bey-Hing
author_facet Yap, Wei Hsum
Cheah, Toh Yang
Yong, Leng Chuan
Chowdhury, Shiplu Roy
Ng, Min Hwei
Kwan, Zhenli
Kong, Chee Kwan
Goh, Bey-Hing
author_sort Yap, Wei Hsum
title Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
title_short Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
title_full Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
title_fullStr Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
title_full_unstemmed Fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
title_sort fibroblast-derived matrices-based human skin equivalent as an in vitro psoriatic model for drug testing
publisher Indian Academy of Sciences
publishDate 2021
url http://eprints.um.edu.my/33999/
_version_ 1738510699150180352
score 13.211869