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.
Adv Healthc Mater. 2017 Jun;6(11). doi: 10.1002/adhm.201601199. Epub 2017 Mar 29.
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.
人们对于开发器官型宫颈模型越来越感兴趣，这种模型使用能够重现生理相关基质微环境和天然宫颈上皮特有组织学的原代宫颈细胞。本文首次报道了一种无支架基质组织的器官型宫颈模型的产生，这种基质组织类似于天然对应物的细胞外基质（ECM）组成和组织，并且具有完全分化良好的上皮。为了实现这一目标，已经制备、表征了人宫颈微组织前体，并将其用作功能构建单元，通过自下而上的方法构建细胞合成的宫颈基质等效物。免疫表型分析、分子和形态分析揭示了基本上皮生物标志物的程度以及胶原和非胶原分子的存在，证明了宫颈组织的天然组织架构和生物学特征得到了重现。这项研究的结果表明，用于产生这些 3D 人宫颈等效物的自下而上技术提供了一种完全功能性的器官型宫颈模型，可作为研究上皮-基质相互作用以及体外测试新疗法的有价值工具。
