The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats
The Regenerative Effect of Portal Vein Injection of Liver Organoids by Retrorsine/Partial Hepatectomy in Rats
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DOI：
10.3390/ijms21010178
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发表时间：
2020-01-01
影响因子：
5.6
通讯作者：
Taniguchi, Hideki
中科院分区：
文献类型：
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作者：
Tsuchida, Tomonori;Murata, Soichiro;Taniguchi, Hideki
在本研究中，我们揭示了肝类器官移植经门静脉是一种安全，有效的方法治疗慢性肝损伤。肝类器官显著重建肝细胞;因此，与反曲马新/部分肝切除术（RS/PH）模型中的单层细胞移植组相比，该组中的肝脏显著增大。肝类器官移植组胆管位于供区，与受体胆管相连。因此，与单层组相比，肝脏中的胆汁重建率显著更高。通过移植肝脏类器官，我们看到70%的受损肝脏被替换。因此，在移植组中，观察到小管反应减少和胎盘谷胱甘肽S-转移酶（GST-p）癌前病变减少。经门静脉注射后，人诱导多能干细胞（hiPSC）衍生的肝类器官显示没有移位到肝外;相反，单层细胞已扩散到肺。hiPSC衍生的肝类器官附着于免疫缺陷RS/PH大鼠的肝脏。这项研究清楚地表明，肝类器官移植通过门静脉是一种安全和有效的方法，用于治疗大鼠慢性肝损伤。
In this study, we reveal that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage. The liver organoids significantly reconstituted the hepatocytes; hence, the liver was significantly enlarged in this group, compared to the monolayer cell transplantation group in the retrorsine/partial hepatectomy (RS/PH) model. In the liver organoid transplantation group, the bile ducts were located in the donor area and connected to the recipient bile ducts. Thus, the rate of bile reconstruction in the liver was significantly higher compared to that in the monolayer group. By transplanting liver organoids, we saw a level of 70% replacement of the damaged liver. Consequently, in the transplantation group, diminished ductular reaction and a decrease of placental glutathione S-transferase (GST-p) precancerous lesions were observed. After trans-portal injection, the human induced pluripotent stem cell (hiPSC)-derived liver organoids revealed no translocation outside the liver; in contrast, the monolayer cells had spread to the lungs. The hiPSC-derived liver organoids were attached to the liver in the immunodeficient RS/PH rats. This study clearly demonstrates that liver organoid transplantation through the portal vein is a safe and effective method for the treatment of chronic liver damage in rats.