Liver Extracellular Matrix Providing Dual Functions of Two-Dimensional Substrate Coating and Three-Dimensional Injectable Hydrogel Platform for Liver Tissue Engineering
Liver Extracellular Matrix Providing Dual Functions of Two-Dimensional Substrate Coating and Three-Dimensional Injectable Hydrogel Platform for Liver Tissue Engineering
复制标题
DOI：
10.1021/bm4015039
复制
发表时间：
2014-01-01
影响因子：
6.2
通讯作者：
Cho, Seung-Woo
中科院分区：
文献类型：
--
作者：
Lee, Jung Seung;Shin, Jisoo;Cho, Seung-Woo
组织或器官的脱细胞可以为组织工程中功能支架的制备提供一种有效的策略。原生细胞外基质的微观结构及其生化成分可以保留在脱细胞基质中，为有效的组织再生提供组织特异性微环境。在这里，我们报道了肝脏细胞外基质（LEM）的多功能性，它可以用于二维（2D）涂层和三维（3D）水凝胶平台，用于培养和移植原代肝细胞。I型胶原蛋白（Col I）通常用于肝细胞培养和移植。在本研究中，LEM与Col I在生物物理和机械特性以及增强细胞活力、分化和肝功能的生物学性能方面进行了比较。通过调节LEM的浓度，可以控制LEM涂层的表面性能和LEM水凝胶的力学性能和凝胶动力学。此外，与Col I水凝胶相比，LEM水凝胶具有更好的弹性性能、快速凝胶化和体积维持能力。LEM包膜可显著改善肝细胞功能，如白蛋白分泌和尿素合成。更有趣的是，LEM涂层上调了人类脂肪来源干细胞的肝脏基因表达，表明这些干细胞的肝脏分化增强。与Col I水凝胶相比，LEM水凝胶在体外和体内均显著提高了原代肝细胞的活力和肝功能。在LEM水凝胶移植的肝细胞中，白蛋白和肝细胞转录因子的表达上调。综上所述，LEM可以通过促进肝细胞的存活和成熟以及干细胞的肝承诺，为肝组织工程中的多种应用提供功能性生物材料平台。本研究证明了脱细胞基质在肝脏组织工程中用于二维涂层和三维水凝胶的可行性。
Decellularization of tissues or organs can provide an efficient strategy for preparing functional scaffolds for tissue engineering. Microstructures of native extracellular matrices and their biochemical compositions can be retained in the decellularized matrices, providing tissue-specific microenvironments for efficient tissue regeneration. Here, we report the versatility of liver extracellular matrix (LEM) that can be used for two-dimensional (2D) coating and three-dimensional (3D) hydrogel platforms for culture and transplantation of primary hepatocytes. Collagen type I (Col I) has typically been used for hepatocyte culture and transplantation. In this study, LEM was compared with Col I in terms of biophysical and mechanical characteristics and biological performance for enhancing cell viability, differentiation, and hepatic functions. Surface properties of LEM coating and mechanical properties and gelation kinetics of LEM hydrogel could be manipulated by adjusting the LEM concentration. In addition, LEM hydrogel exhibited improved elastic properties, rapid gelation, and volume maintenance compared to Col I hydrogel. LEM coating significantly improved hepatocyte functions such as albumin secretion and urea synthesis. More interestingly, LEM coating upregulated hepatic gene expression of human adipose-derived stem cells, indicating enhanced hepatic differentiation of these stem cells. The viability and hepatic functions of primary hepatocytes were also significantly improved in LEM hydrogel compared to Col I hydrogel both in vitro and in vivo. Albumin and hepatocyte transcription factor expression was upregulated in hepatocytes transplanted in LEM hydrogels. In conclusion, LEM can provide functional biomaterial platforms for diverse applications in liver tissue engineering by promoting survival and maturation of hepatocytes and hepatic commitment of stem cells. This study demonstrates the feasibility of decellularized matrix for both 2D coating and 3D hydrogel in liver tissue engineering.