Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
Advanced Photonics and Biosensing Open Innovation Laboratory, National Institute of Advanced Industrial Science and Technology (AIST), Central 5-41, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan.
Sci Rep. 2020 Apr 14;10(1):5646. doi: 10.1038/s41598-020-62286-3.
Although various production methods for 3D vascularised tissues have been developed, constructing capillary-like structures branching from perfusable large channels remains difficult. This study describes a method to fabricate tube-shaped 3D liver-like tissue (tubular liver tissue) with large channels and capillary-like structures using a perfusion device. The perfusion device functions as an interface between the tissue and an external pump, as it has connectors equipped with anchors that hold the tissue in response to its shrinkage, which is accompanied by the self-organisation of capillary-like structures. Histological analysis revealed that perfusion via the large channel induced capillary formation around the channel and maintained proper tissue functions. Accompanied by structural examinations, global gene expression analysis supported this finding; specifically, genes involved in angiogenesis were enriched in the perfused condition. Furthermore, we confirmed the penetrability of the capillary-like structures by infusing India ink, as well as substance exchange by measuring the amounts of secreted albumin. These lines of evidence indicate that our method can be used to construct 3D tissues, which is useful for fields of in vitro tissue regeneration for drug development and regenerative medicine.
虽然已经开发出了各种制造 3D 血管化组织的方法，但构建从可灌注的大通道分支出来的毛细血管样结构仍然很困难。本研究描述了一种使用灌注装置制造具有大通道和毛细血管样结构的管状肝样组织（管状肝组织）的方法。该灌注装置作为组织与外部泵之间的接口，因为它具有配备有锚定件的连接器，这些连接器会响应组织的收缩而固定组织，从而伴随着毛细血管样结构的自组织。组织学分析表明，通过大通道的灌注诱导了围绕通道的毛细血管形成，并维持了适当的组织功能。伴随着结构检查，整体基因表达分析支持了这一发现；具体而言，参与血管生成的基因在灌注条件下富集。此外，我们通过注入印度墨水证实了毛细血管样结构的可渗透性，并通过测量分泌的白蛋白的量证实了物质交换。这些证据表明，我们的方法可用于构建 3D 组织，这对于药物开发和再生医学领域的体外组织再生非常有用。
