Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets
Engineering functional two- and three-dimensional liver systems in vivo using hepatic tissue sheets
复制标题
DOI：
10.1038/nm1576
复制
发表时间：
2007-07-01
期刊：
影响因子：
82.9
通讯作者：
Nakajima, Yoshiyuki
中科院分区：
文献类型：
--
作者：
Ohashi, Kazuo;Yokoyama, Takashi;Nakajima, Yoshiyuki
利用原代肝细胞进行肝组织工程已被认为是治疗多种肝病的一种有价值的新方法。然而，目前临床上可行的肝组织工程方法的发展主要受到移植肝细胞间接触不足的阻碍。我们开发了一种方法，利用培养在温度敏感表面的分离的原代肝细胞，设计出均匀连续的肝组织薄片。将肝组织片状移植到皮下间隙，可以有效地植入周围细胞，形成稳定存在超过200d的二维肝组织。工程肝组织还显示出一些肝脏特异性功能的特征。此外，当肝组织片在体内分层时，也可以设计出具有持久存活率的三维微型肝脏系统。这项用于肝脏组织工程的技术简单、微创，并且不含潜在的免疫原性生物可降解支架。
Hepatic tissue engineering using primary hepatocytes has been considered a valuable new therapeutic modality for several classes of liver diseases. Recent progress in the development of clinically feasible liver tissue engineering approaches, however, has been hampered mainly by insufficient cell-to-cell contact of the engrafted hepatocytes. We developed a method to engineer a uniformly continuous sheet of hepatic tissue using isolated primary hepatocytes cultured on temperature-responsive surfaces. Sheets of hepatic tissue transplanted into the subcutaneous space resulted in efficient engraftment to the surrounding cells, with the formation of two-dimensional hepatic tissues that stably persisted for longer than 200 d. The engineered hepatic tissues also showed several characteristics of liver-specific functionality. Additionally, when the hepatic tissue sheets were layered in vivo, three-dimensional miniature liver systems having persistent survivability could be also engineered. This technology for liver tissue engineering is simple, minimally invasive and free of potentially immunogenic biodegradable scaffolds.