Hasenberg Tobias, Mühleder Severin, Dotzler Andrea, Bauer Sophie, Labuda Krystyna, Holnthoner Wolfgang, Redl Heinz, Lauster Roland, Marx Uwe
Technische Universität Berlin, Medical Biotechnology, TIB 4/4-2, Gustav-Meyer-Allee 25, 13355 Berlin, Germany; TissUse GmbH, Markgrafenstraße 18, 15528 Spreenhagen, Germany.
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstraße 13, 1200 Vienna, Austria; Austrian Cluster for Tissue Regeneration, Vienna, Austria.
J Biotechnol. 2015 Dec 20;216:1-10. doi: 10.1016/j.jbiotec.2015.09.038. Epub 2015 Oct 3.
Current microfluidic chip-based tissue culture systems lack a capillary endothelial vessel system, which would enable perfusion with blood. We utilise spatial cell cultures to populate a perfused multi-organ-chip platform-a microfluidic device recently introduced for substance testing. Complete biological vascularization of such culture systems is vital to properly emulate physiological tissue behaviour. In this study, we incorporated a fibrin scaffold into the two-organ-chip design. Herein, adipose-derived stromal cells (ASCs) directed human umbilical vein endothelial cells (HUVECs) to organise into tube-like structures. The ASCs induced tube formation of HUVECs in static and dynamic conditions. The replacement of full medium enriched with growth factors and foetal calf serum with basal medium resulted in viable cells with similar gene expression profiles. We regard this as a prerequisite for studies with organ constructs that have a need for a different medium formulation. Furthermore, we here address stability issues of the fibrin gel and fibrin composition for optimal microvessel formation.
当前基于微流控芯片的组织培养系统缺乏能够实现血液灌注的毛细血管内皮血管系统。我们利用空间细胞培养技术在一个灌注多器官芯片平台上进行细胞接种,该平台是一种最近推出的用于物质测试的微流控装置。这种培养系统的完全生物血管化对于正确模拟生理组织行为至关重要。在本研究中,我们将纤维蛋白支架纳入双器官芯片设计中。在此,脂肪来源的基质细胞(ASC)引导人脐静脉内皮细胞(HUVEC)组织形成管状结构。ASC在静态和动态条件下均诱导HUVEC形成管腔。用基础培养基替代富含生长因子和胎牛血清的完全培养基后,细胞仍具有活力且基因表达谱相似。我们认为这是对需要不同培养基配方的器官构建体进行研究的先决条件。此外,我们在此探讨了纤维蛋白凝胶的稳定性问题以及用于优化微血管形成的纤维蛋白组成。