title: In vitro M-like cells genesis through a tissue-engineered triple-culture intestinal model.
abstract: 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.
authors: 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.|ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, Porto, 4050-313, Portugal.
authors: Francisca
authors: F
authors: Araújo
authors: 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.|FEUP-Faculdade de Engenharia, University of Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal.
authors: Carla
authors: C
authors: Pereira
authors: 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.|FEUP-Faculdade de Engenharia, University of Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal.
authors: Joana
authors: J
authors: Costa
authors: 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.
authors: Cristina
authors: C
authors: Barrias
authors: 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.|ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Rua de Jorge Viterbo Ferreira, Porto, 4050-313, Portugal.|FEUP-Faculdade de Engenharia, University of Porto, Rua Dr. Roberto Frias, Porto, 4200-465, Portugal.
authors: Pedro L
authors: PL
authors: Granja
authors: 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.|CESPU-Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Instituto Universitário de Ciências da Saúde, Rua Central de Grandra, 1317, Gandra, 4585-116, Portugal.
authors: Bruno
authors: B
authors: Sarmento
mesh_terms: D000938:Antigen-Presenting Cells / Q000166:cytology / Q000378:metabolism*; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018938:Caco-2 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism*; D023822:Tissue Engineering
keywords: Caco-2 cells; HT29-MTX cells; M-like cells; follicle-associated epithelium; tissue-engineered in vitro model