Structural and Functional Validation of a Full-Thickness Self-Assembled Skin Equivalent for Disease Modeling
Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a se...
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Published in | Pharmaceutics Vol. 14; no. 6; p. 1211 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
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07.06.2022
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Abstract | Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases. |
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AbstractList | Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air–liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases. Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases.Recently, various types of in vitro-reconstructed 3D skin models have been developed for drug testing and disease modeling. Herein, we structurally and functionally validated a self-assembled reconstructed skin equivalent (RSE) and developed an IL-17a-induced in vitro psoriasis-like model using a self-assembled RSE. The tissue engineering approach was used to construct the self-assembled RSE. The dermal layer was generated using fibroblasts secreting their own ECM, and the epidermal layer was reconstructed by seeding keratinocytes on the dermal layer. To generate the psoriatic model, IL-17A was added to the culture medium during the air-liquid interface culture period. Self-assembled RSE resulted in a fully differentiated epidermal layer, a well-established basement membrane, and dermal collagen deposition. In addition, self-assembled RSE was tested for 20 reference chemicals according to the Performance Standard of OECD TG439 and showed overall sensitivity, specificity, and accuracy of 100%, 90%, and 95%, respectively. The IL-17a-treated psoriatic RSE model exhibited psoriatic epidermal characteristics, such as epidermal hyperproliferation, parakeratosis, and increased expression of KRT6, KRT17, hBD2, and S100A9. Thus, our results suggest that a self-assembled RSE that structurally and functionally mimics the human skin has a great potential for testing various drugs or cosmetic ingredients and modeling inflammatory skin diseases. |
Author | Simard-Bisson, Carolyne Shin, Jung U Kim, A Ram Mok, Bo Ram Shon, Su-Ji Martel, Israël Germain, Lucie Kim, Dong Hyun |
AuthorAffiliation | 2 Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada; carolyne.simard-bisson@crchudequebec.ulaval.ca (C.S.-B.); israel.martel@crchudequebec.ulaval.ca (I.M.); lucie.germain@fmed.ulaval.ca (L.G.) 1 Department of Biomedical Science, CHA University, Seongnam 13488, Korea; mokbbo@gmail.com (B.R.M.); orange11026@naver.com (S.-J.S.); tmfdkdjssl@hanmail.net (A.R.K.) 3 Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea; terios92@cha.ac.kr |
AuthorAffiliation_xml | – name: 1 Department of Biomedical Science, CHA University, Seongnam 13488, Korea; mokbbo@gmail.com (B.R.M.); orange11026@naver.com (S.-J.S.); tmfdkdjssl@hanmail.net (A.R.K.) – name: 2 Centre de Recherche en Organogénèse Expérimentale de l’Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada; carolyne.simard-bisson@crchudequebec.ulaval.ca (C.S.-B.); israel.martel@crchudequebec.ulaval.ca (I.M.); lucie.germain@fmed.ulaval.ca (L.G.) – name: 3 Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea; terios92@cha.ac.kr |
Author_xml | – sequence: 1 givenname: Bo Ram surname: Mok fullname: Mok, Bo Ram organization: Department of Biomedical Science, CHA University, Seongnam 13488, Korea – sequence: 2 givenname: Su-Ji surname: Shon fullname: Shon, Su-Ji organization: Department of Biomedical Science, CHA University, Seongnam 13488, Korea – sequence: 3 givenname: A Ram orcidid: 0000-0002-5458-1985 surname: Kim fullname: Kim, A Ram organization: Department of Biomedical Science, CHA University, Seongnam 13488, Korea – sequence: 4 givenname: Carolyne surname: Simard-Bisson fullname: Simard-Bisson, Carolyne organization: Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada – sequence: 5 givenname: Israël surname: Martel fullname: Martel, Israël organization: Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada – sequence: 6 givenname: Lucie orcidid: 0000-0001-8883-6491 surname: Germain fullname: Germain, Lucie organization: Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, and Department of Surgery, Faculty of Medicine, Université Laval, CHU de Québec-Université Laval Research Centre, Québec, QC G1J1Z4, Canada – sequence: 7 givenname: Dong Hyun surname: Kim fullname: Kim, Dong Hyun organization: Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea – sequence: 8 givenname: Jung U surname: Shin fullname: Shin, Jung U organization: Department of Dermatology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam 13497, Korea |
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StartPage | 1211 |
SubjectTerms | 3D skin Collagen Digital cameras Extracellular matrix Fibroblasts Medical research Morphology Psoriasis psoriasis model reconstructed skin Scanning electron microscopy self-assembly tissue engineering Skin diseases |
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Title | Structural and Functional Validation of a Full-Thickness Self-Assembled Skin Equivalent for Disease Modeling |
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