The physiological performance of a three-dimensional model that mimics the microenvironment of the small intestine.

Our focus was to develop a three-dimensional (3D) human dynamic in vitro tissue model that mimics the natural microenvironment of the small intestine. We co-cultured human Caco-2 cells with primary-isolated human microvascular endothelial cells (hMECs) on decellularized porcine jejunal segments within a custom-made dynamic bioreactor system that resembles the apical and basolateral side of the intestine for up to 14 days. The obtained data were compared to results generated using routine static Caco-2 assays. We performed histology and immunohistochemistry. Permeability was measured using directed transport studies. Histological analyses revealed that in tissue-engineered segments, which had been cultured under dynamic conditions, the Caco-2 cells showed a high-prismatic morphology, resembling normal primary enterocytes within their native environment. We further identified that the transport of low permeable substances, such as fluorescein and desmopressin increased within the dynamic bioreactor cultures. Immunohistochemical staining showed a significantly higher expression of the efflux transport p-glycoprotein (p-gp) under dynamic culture conditions when compared to the static cultures. We conclude that the integration of physiological parameters is crucial for the establishment of a reliable 3D intestinal in vitro model, which enables the simulation of drug transport over the gut-blood-barrier in a simplified way.

RETRACTED: Vascularised human tissue models: a new approach for the refinement of biomedical research.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Author(s). (a) The authors have duplicated at least one figure from a paper that had already appeared in: • Engineered Liver-Like Tissue on a Capillarized Matrix for Applied Research. TISSUE ENGINEERING; Volume 13, Number 11, 2007 Engineered Liver-Like Tissue on a Capillarized Matrix for Applied Research. KIRSTIN LINKE, JOHANNA SCHANZ, JAN HANSMANN, THORSTEN WALLES, HERWIG BRUNNER, & HEIKE MERTSCHING Apparently, no permission was obtained to re-publish the image, as the authors did not provide us with a copy of a release issued by Mary Ann Liebert Inc. with an authorization to re-publish the figure initially published in Linke et al. (2007) in J. Biotechnology. In this case, this infringes on the copyright of Mary Ann Liebert Inc. The authors stated on Feb. 11 2017 in an email to the Editor in Chief: "Between 2007 and 2010 we modified the culture conditions in out (Chief Editor comment: this means "our") tissue models. These changes did not influence the morphology and 3 D arrangement of the cells. However, they changed the long term function of out (Chief Editor comment: this means "our") tissue models." Therefore, they implied that the figures shown in the 2010 paper demonstrate that there were no changes in the "morphology and 3 D arrangement of the cells" when comparing the culture conditions. It would, in our opinion, be impossible to demonstrate the similarities in the two different culture conditions by using the same figures as in the 2007 article, as both instances only show the result of the original culture condition. (b) The authors have also (self)plagiarized significant text sections from: • Genes Nutr. 2009 September; 4(3): 165-172 Penza, Jeremic, Montani, Unkila, Caimi, Mazzoleni, Diego Di Lorenzo PMCID: PMC2745740 DOI: 10.1007/s12263-009-0214-7 Springer-Verlag 2009 • Van den Belt K, Berckmans P, Vangenechten C, Verheyen R, Witters H (2004) Comparative study on the in vitro/in vivo estrogenic potencies of 17beta-estradiol, estrone, 17alpha-ethynylestradiol and nonylphenol. Aquat Toxicol 66(2):183­195 • Generation and Transplantation of an Autologous Vascularized Bioartificial Human Tissue. (2009) Clinical and Translational Research Transplantation; 27 July 2009 - Volume 88 - Issue 2 - pp 203-210 Heike Mertsching, Johanna Schanz, Volker Steger, Markus Schandar, Martin Schenk, Jan Hansmann, Iris Dally, Godehard Friedel, & Thorsten Walles One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data and text should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process