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

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• 作者：Jacqueline Pusch^a ; Miriam Votteler^a ; ^b ; Stella Gö ; hler^a ; Jasmin Engl^a ; Martina Hampel^a ; ^c ; Heike Walles^a ; ^d ; Katja Schenke-Layland^a ; ^b ; ^{katja.schenke-layland@igb.fraunhofer.de"" rel=""nofollow}
• 关键词：Organ culture ; In vitro test ; Co-culture ; Cell morphology ; ECM (extracellular matrix) ; Epithelial cell
• 刊名：Biomaterials
• 出版年：2011
• 出版时间：October 2011
• 年：2011
• 卷：32
• 期：30
• 页码：7469-7478
• 全文大小：2859 K

文摘

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.