title: Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies.
abstract: Caco-2 based cell models have been the gold standard in vitro method to study intestinal drug permeability, despite the absence of many important features with major influence in the drug absorption mechanism. In the present work, a triple co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic in a closely way the human intestinal epithelium, presenting the main components in the process of drug absorption, namely the absorptive cells that resemble enterocytes, mucus producers cells and cells able to induce M-cell phenotype on Caco-2 cells. All the three cell lines maintained their function when cultured together with each other being, thus, an asset to new orally administrated drugs development. The seeding ratio of 90:10 between Caco-2 and HT29-MTX showed to be the best to achieve physiological proportions after cells maturation and differentiation in culture. The formation of M-cells phenotype from enterocytes was identified for the first time in a co-culture system comprising Caco-2 and HT29-MTX cells through immunocytochemical techniques. Thus, the triple co-culture model presented in the herein work is a good and reliable alternative to the in vitro methods already existents for the study of drugs permeability.
authors.affiliation: Centro de Investigação em Ciências da Saúde (CICS), Instituto Superior de Ciências da Saúde-Norte, CESPU, Rua Central de Gandra, 1317, 4585-116 Gandra, Portugal; INEB - Instituto de Engenharia Biomédica, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Francisca
authors.initials: F
authors.lastname: Araújo
authors.forename: Bruno
authors.initials: B
authors.lastname: Sarmento
mesh_terms: D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000502:physiology; D045744:Cell Line, Tumor; D018920:Coculture Techniques / Q000379:methods; D020895:Enterocytes / Q000378:metabolism / Q000502:physiology; D019073:HT29 Cells; D006801:Humans; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000502:physiology; D007422:Intestines / Q000502:physiology*; D010539:Permeability
keywords: Caco-2 cells; Co-culture; HT29-MTX cells; In vitro model; Intestinal permeability; Raji B cells