Araújo Francisca, Pereira Carla, Costa Joana, Barrias Cristina, Granja Pedro L, Sarmento Bruno
I3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal.
INEB-Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, Porto, 4150-180, Portugal.
J Biomed Mater Res B Appl Biomater. 2016 May;104(4):782-8. doi: 10.1002/jbm.b.33508. Epub 2015 Aug 27.
Although fewer in number, M-cells are considered antigen sampling cells, acting as a gateway for antigens from the gut lumen and presenting an impressive aptitude for particle transcytosis. These features make M-cells attractive targets for oral drug delivery studies, but this has been poorly explored. New and reproducible tissue-like in vitro models for studying intestinal sampling and permeability mechanisms are needed. The combination of different cell players in such models offers improved microenvironments with higher physiologic relevance. Here, a tissue-engineered model was established, by co-culturing Caco-2 absorptive cells, HT29-MTX mucus-producing cells and Raji B lymphocytes. After 3 weeks of cell co-culture, the presence of M-like cells was evidenced by the loss of brush-border organization, detected by the lack of microvilli. The triple-culture model showed to be efficient for insulin transport, a process that was influenced by the tightness of junctions between epithelial cells and the presence of mucus and M-like cells. Ultimately, the proposed tissue-engineered model provides a more complete and reliable tool to perform drug permeability tests, as compared to traditional models, and may also find applicability as an in vitro system to study transdifferentiation mechanisms of M cells.
尽管数量较少，但M细胞被认为是抗原采样细胞，充当来自肠腔的抗原的通道，并表现出令人印象深刻的颗粒转胞吞能力。这些特性使M细胞成为口服药物递送研究的有吸引力的靶点，但这方面的研究还很少。需要新的、可重复的体外组织样模型来研究肠道采样和渗透机制。在这些模型中不同细胞成分的组合提供了具有更高生理相关性的改善的微环境。在此，通过共培养Caco-2吸收细胞、HT29-MTX黏液分泌细胞和Raji B淋巴细胞建立了一种组织工程模型。细胞共培养3周后，通过微绒毛的缺失检测到刷状缘结构的丧失，从而证明了M样细胞的存在。三重培养模型显示对胰岛素转运有效，这一过程受上皮细胞间连接的紧密性以及黏液和M样细胞的存在影响。最终，与传统模型相比，所提出的组织工程模型为进行药物渗透性测试提供了一个更完整、更可靠的工具，并且还可能作为研究M细胞转分化机制的体外系统找到应用。
