A novel evaluation system for whole-organ-engineered liver graft by ex vivo application to a highly reproducible hepatic failure rat model
A novel evaluation system for whole-organ-engineered liver graft by ex vivo application to a highly reproducible hepatic failure rat model
复制标题
通过离体应用于高度可重复的肝衰竭大鼠模型的全器官工程肝移植的新型评估系统
DOI：
10.1007/s10047-019-01106-6
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发表时间：
2019
影响因子：
1.3
通讯作者：
Ijima Hiroyuki
中科院分区：
文献类型：
--
作者：
Sakamoto Hiroki;Shirakigawa Nana;Bual Ronald Perocho;Fukuda Yukako;Nakamura Shunsuke;Miyata Tatsunori;Yamao Takanobu;Yamashita Yo-ichi;Baba Hideo;Ijima Hiroyuki
近年来，以脱细胞肝为模板构建肝移植物的研究受到广泛关注。然而，构建的肝移植物在肝功能衰竭中的治疗效果尚未得到评价。因此，我们的目的是开发一种新的评价系统，证明肝衰竭动物中构建的肝移植物的疗效。首先，我们通过结合80%肝部分切除和热缺血建立了一个高度可重复的肝衰竭大鼠模型。在该模型中，严重程度可以通过热缺血期来控制。我们还通过脱细胞肝的再细胞化构建了肝移植物，并在体外证实了移植物中的氨代谢功能是肝功能衰竭恢复的最重要功能之一。然后将移植物应用于我们开发的肝功能衰竭大鼠模型，使用血液体外循环系统。在这项应用中，移植物代谢了肝衰竭动物血液中的氨，因此表明对治疗肝衰竭有效。综上所述，我们建立了一个新的评估系统，用于全器官工程肝移植作为移植的前期阶段。该系统有望为构建的肝移植物的疗效提供更多的信息。
In recent years, studies on liver graft construction using the decellularized liver as a template for transplantation therapy have attracted much attention. However, the therapeutic effect of constructed liver grafts in hepatic failure has not been evaluated. Therefore, we aimed to develop a novel evaluation system demonstrating the curative effect of a constructed liver graft in animals with hepatic failure. First, we developed a highly reproducible rat model of hepatic failure by combining 80% partial hepatectomy with warm ischemia. In this model, severity could be controlled by the warm ischemic period. We also constructed a liver graft by recellularization of decellularized liver, and confirmed the ammonia metabolic function in the graft in vitro as one of the most important functions for recovery from hepatic failure. The graft was then applied to our developed hepatic failure rat model using a blood extracorporeal circulation system. In this application, the graft metabolized the ammonia in the blood of animals with hepatic failure and was thus suggested to be effective for the treatment of hepatic failure. In summary, a novel evaluation system for whole-organ-engineered liver graft as a preliminary stage of transplantation was developed. This system was expected to provide much information about the curative effect of a constructed liver graft.