Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering
Induced pluripotent stem cell-derived hepatocytes and endothelial cells in multi-component hydrogel fibers for liver tissue engineering
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DOI：
10.1016/j.biomaterials.2014.04.011
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发表时间：
2014-07-01
期刊：
影响因子：
14
通讯作者：
Wan, Andrew C. A.
中科院分区：
文献类型：
--
作者：
Du, Chan;Narayanan, Karthikeyan;Wan, Andrew C. A.
肝组织工程需要合适的细胞来源，以空间限定的方式在其小生境微环境内组装细胞的方法，以及体内构建体的血管化以维持肝细胞活力和功能。最近，我们已经开发了将细胞包封在多组分水凝胶纤维中的单独结构域内的方法和组装纤维以形成3D图案化组织构建体的方法。在目前的工作中，我们已经结合这些方法来封装肝细胞和内皮细胞在其特定的壁龛，并组装成内皮化的肝组织结构。通过分化人重组蛋白诱导的人多能干细胞平行获得肝细胞和内皮细胞，从而产生含有遗传上相同的内皮和实质元件的构建体。我们能够证明，在支架中的内皮细胞的存在下，显着改善肝细胞的功能，在体外和促进血管化的支架植入小鼠部分肝切除模型时。体内研究进一步断言，支架与宿主脉管系统的整合已经发生，如小鼠血清中人白蛋白的存在所证明的。(C)2014爱思唯尔有限公司版权所有。
Liver tissue engineering requires a suitable cell source, methodologies to assemble the cells within their niche microenvironments in a spatially defined manner, and vascularization of the construct in vivo for maintenance of hepatocyte viability and function. Recently, we have developed methods of encapsulating cells within separate domains in multi-component hydrogel fibers and methods of assembling fibers to form 3D-patterned tissue constructs. In the present work, we have combined these approaches to encapsulate hepatocytes and endothelial cells within their specific niches, and to assemble them into endothelialized liver tissue constructs. The hepatocytes and endothelial cells were obtained in parallel by differentiating human recombinant protein-induced human pluripotent stem cells, resulting in a construct which contained genetically identical endothelial and parenchymal elements. We were able to demonstrate that the presence of endothelial cells in the scaffold significantly improved hepatocyte function in vitro and facilitated vascularization of the scaffold when implanted in a mouse partial hepatectomy model. The in vivo studies further asserted that integration of the scaffold with host vasculature had occurred, as demonstrated by the presence of human albumin in the mouse serum. (C) 2014 Elsevier Ltd. All rights reserved.