title: An Engineered Cell-Instructive Stroma for the Fabrication of a Novel Full Thickness Human Cervix Equivalent In Vitro.
abstract: There is a growing interest for developing organotypic cervical models by using primary cervical cells that are able to reproduce the physiological relevant stromal microenvironment and the distinctive histology of the native cervical epithelium. Here for the first time it is reported the production of an organotypic cervical model featured by a scaffold-free stromal tissue resembling the extracellular matrix (ECM) composition and organization of the native counterpart as well as a completely well-differentiated epithelium. To reach this aim, human cervical microtissue precursors have been produced, characterized, and used as functional building units to fabricate a cell-synthesized cervical stroma equivalent by means of a bottom-up approach. Immunotypization, and molecular and morphological analyses reveal the extent of fundamental epithelial biomarkers and the presence of collagen and noncollagenous molecules, demonstrating that the natural tissue architecture and biological characteristics of cervical tissues are reproduced. The results of this study suggest that the bottom-up technology used to produce these 3D human cervical equivalents provides a fully functional organotypic cervical model that may be used as a valuable tool to investigate the epithelial-stromal interactions as well as for testing new therapeutics in vitro.
authors.affiliation: Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Naples, Italy.
authors.forename: Vincenza
authors.initials: V
authors.lastname: De Gregorio
authors.affiliation: Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Naples, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Imparato
authors.affiliation: Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Urciuolo
authors.affiliation: Molecular Biology and Viral Oncology Unit Istituto Nazionale, Tumori IRCCS "Fondazione Pascale", 80131, Naples, Italy.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Tornesello
authors.affiliation: Molecular Biology and Viral Oncology Unit Istituto Nazionale, Tumori IRCCS "Fondazione Pascale", 80131, Naples, Italy.
authors.forename: Clorinda
authors.initials: C
authors.lastname: Annunziata
authors.affiliation: Molecular Biology and Viral Oncology Unit Istituto Nazionale, Tumori IRCCS "Fondazione Pascale", 80131, Naples, Italy.
authors.forename: Franco M
authors.initials: FM
authors.lastname: Buonaguro
authors.affiliation: Center for Advanced Biomaterials for HealthCare@CRIB, Istituto Italiano di Tecnologia, Largo Barsanti e Matteucci 53, 80125, Naples, Italy.|Molecular Biology and Viral Oncology Unit Istituto Nazionale, Tumori IRCCS "Fondazione Pascale", 80131, Naples, Italy.|Department of Chemical Materials and Industrial Production (DICMAPI), University of Naples Federico II, P.leTecchio 80, 80125, Naples, Italy.
authors.forename: Paolo A
authors.initials: PA
authors.lastname: Netti
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000166:cytology / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017154:Stromal Cells / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering
keywords: ECM; bottom-up tissue engineering; gelatin microscaffold; organotypic cervical model; primary human cervical keratinocytes