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Medium-term culture of normal human oral mucosa: a novel three-dimensional model to study the effectiveness of drugs administration

Medium-term culture of normal human oral mucosa: a novel three-dimensional model to study the effectiveness of drugs administration
Medium-term culture of normal human oral mucosa: a novel three-dimensional model to study the effectiveness of drugs administration
Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an artificial extracellular matrix (Matrigel™ ), allowing the interactions required for proper differentiation of the various citotypes which form the mucosal layer. Biopsies of human oral mucosa, in fragments of about 0.5 mm3, were placed onto 6.5mm Transwells, covered with Matrigel™ and grown in a specific culture medium. A gradual formation of an architectural structure similar to that of the in vivo oral mucosa was observed. Transmission electron and confocal microscopy were employed to characterize the newly developed model: the cell components (keratinocytes and fibroblasts) differentiated properly within the outgrowth and reconstituted, in vitro, the physiological structure of the human oral mucosa, including a stratified non-keratinized squamous layer composed of four different layers, a proper basal membrane and a lamina propria where fibroblasts produce ECM. Moreover, keratinocytes expressed CK5, CK13, CK19 and E-cadherin, whereas fibroblasts expressed collagen type I and IV, laminin and fibronectin. 3D outgrowths could be considered a valid alternative to animal models, and provide useful information for researchers interested in studying the responses of the human oral mucosa to locally delivered drugs or other exogenous treatments.
5421-5430
Bucchieri, Fabio
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Fucarino, Alberto
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Marino Gammazza, Antonella
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Pitruzzella, Alessandro
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Marciano, Vito
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Paderni, Carlo
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De Caro, Viviana
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Siragusa, Maria Gabriella
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Lo Muzio, Lorenzo
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Holgate, Stephen T.
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Davies, Donna E.
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Farina, Felicia
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Zummo, Giovanni
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Kudo, Yasusei
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Giannola, Italo Libero
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Campisi, Giuseppina
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Bucchieri, Fabio
d5c6c38a-8b02-4a37-afb0-c272033cb0d2
Fucarino, Alberto
95c722bb-5f4d-43b7-a173-c72e40b3c792
Marino Gammazza, Antonella
b8683acd-7d10-4e5a-9224-ff7b283d7a65
Pitruzzella, Alessandro
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Marciano, Vito
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Paderni, Carlo
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De Caro, Viviana
f35398ec-c716-4a86-bd9f-b61e6cfbb84b
Siragusa, Maria Gabriella
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Lo Muzio, Lorenzo
f513a351-d1e6-4c99-a39a-e187f6e489de
Holgate, Stephen T.
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Davies, Donna E.
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Farina, Felicia
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Zummo, Giovanni
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Kudo, Yasusei
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Giannola, Italo Libero
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Campisi, Giuseppina
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Bucchieri, Fabio, Fucarino, Alberto, Marino Gammazza, Antonella, Pitruzzella, Alessandro, Marciano, Vito, Paderni, Carlo, De Caro, Viviana, Siragusa, Maria Gabriella, Lo Muzio, Lorenzo, Holgate, Stephen T., Davies, Donna E., Farina, Felicia, Zummo, Giovanni, Kudo, Yasusei, Giannola, Italo Libero and Campisi, Giuseppina (2012) Medium-term culture of normal human oral mucosa: a novel three-dimensional model to study the effectiveness of drugs administration. Current Pharmaceutical Design, 18 (34), 5421-5430. (doi:10.2174/138161212803307482). (PMID:22632390)

Record type: Article

Abstract

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an artificial extracellular matrix (Matrigel™ ), allowing the interactions required for proper differentiation of the various citotypes which form the mucosal layer. Biopsies of human oral mucosa, in fragments of about 0.5 mm3, were placed onto 6.5mm Transwells, covered with Matrigel™ and grown in a specific culture medium. A gradual formation of an architectural structure similar to that of the in vivo oral mucosa was observed. Transmission electron and confocal microscopy were employed to characterize the newly developed model: the cell components (keratinocytes and fibroblasts) differentiated properly within the outgrowth and reconstituted, in vitro, the physiological structure of the human oral mucosa, including a stratified non-keratinized squamous layer composed of four different layers, a proper basal membrane and a lamina propria where fibroblasts produce ECM. Moreover, keratinocytes expressed CK5, CK13, CK19 and E-cadherin, whereas fibroblasts expressed collagen type I and IV, laminin and fibronectin. 3D outgrowths could be considered a valid alternative to animal models, and provide useful information for researchers interested in studying the responses of the human oral mucosa to locally delivered drugs or other exogenous treatments.

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Published date: 2012
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 359870
URI: https://eprints.soton.ac.uk/id/eprint/359870
PURE UUID: c30db28d-cd44-4808-85d1-bcd084b01b92

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Date deposited: 15 Nov 2013 13:48
Last modified: 18 Jul 2017 03:17

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Contributors

Author: Fabio Bucchieri
Author: Alberto Fucarino
Author: Antonella Marino Gammazza
Author: Alessandro Pitruzzella
Author: Vito Marciano
Author: Carlo Paderni
Author: Viviana De Caro
Author: Maria Gabriella Siragusa
Author: Lorenzo Lo Muzio
Author: Donna E. Davies
Author: Felicia Farina
Author: Giovanni Zummo
Author: Yasusei Kudo
Author: Italo Libero Giannola
Author: Giuseppina Campisi

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