Mathematical-model-guided development of full-thickness epidermal equivalent
| Autor: | Yusuke Yasugahira, Masaaki Uesaka, Shinobu Nakanishi, Junichi Kumamoto, Sumiko Denda, Mio Makita, Masaharu Nagayama, Mitsuhiro Denda, Yasuaki Kobayashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Keratinocytes
Male 0301 basic medicine Polyesters Cell Culture Techniques lcsh:Medicine Filaggrin Proteins Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Drug Development Stratum corneum medicine Humans Computer Simulation Claudin lcsh:Science Cells Cultured Barrier function Cell Proliferation Skin Artificial Transepidermal water loss Multidisciplinary Tissue Engineering Tissue Scaffolds integumentary system Chemistry Textiles lcsh:R Infant Newborn Organ Size Models Theoretical 030104 developmental biology medicine.anatomical_structure Chondroitin sulfate proteoglycan 030220 oncology & carcinogenesis Biophysics Loricrin lcsh:Q Epidermis Filaggrin |
| Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-8 (2018) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Epidermal equivalents prepared with passaged keratinocytes are typically 10–20 μm thick, whereas intact human epidermis is up to 100 μm thick. Our established mathematical model of epidermal homeostasis predicted that the undulatory pattern of the papillary layer beneath the epidermis is a key determinant of epidermal thickness. Here, we tested this prediction by seeding human keratinocytes on polyester textiles with various fiber-structural patterns in culture dishes exposed to air, aiming to develop a more physiologically realistic epidermal model using passaged keratinocytes. Textile substrate with fiber thickness and inter-fiber distance matching the computer predictions afforded a three-dimensional epidermal-equivalent model with thick stratum corneum and intercellular lamellar lipid structure. The basal layer structure was similar to that of human papillary layer. Cells located around the textile fibers were proliferating, as indicated by BrdU and YAP (Yes-associated protein) staining and expression of melanoma-associated chondroitin sulfate proteoglycan. Filaggrin, loricrin, claudin 1 and ZO-1 were all appropriately expressed. Silencing of transcriptional coactivator YAP with siRNA disturbed construction of the three-dimensional structure. Measurement of trans-epidermal water loss (TEWL) indicated that the model has excellent barrier function. Our results support the idea that mathematical modeling of complex biological processes can have predictive ability and practical value. |
| Databáze: | OpenAIRE |
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