Ono Yoshihiro, Pérez-Gutiérrez Angelica, Yovchev Mladen I, Matsubara Kentaro, Yokota Shinichiro, Guzman-Lepe Jorge, Handa Kan, Collin de l'Hortet Alexandra, Thomson Angus W, Geller David A, Yagi Hiroshi, Oertel Michael, Soto-Gutierrez Alejandro
1 Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.2 Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, Japan.3 Thomas E Starzl Transplantation Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA.4 McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA.
Transplantation. 2017 Jan;101(1):92-100. doi: 10.1097/TP.0000000000001511.
Auxiliary partial liver transplantation (APLT) in humans is a therapeutic modality used especially to treat liver failure in children or congenital metabolic disease. Animal models of APLT have helped to explore therapeutic options. Though many groups have suggested improvements, standardizing the surgical procedure has been challenging. Additionally, the question of whether graft livers are reconstituted by recipient-derived cells after transplantation has been controversial. The aim of this study was to improve experimental APLT in rats and to assess cell recruitment in the liver grafts.
To inhibit recipient liver regeneration and to promote graft regeneration, we treated recipients with retrorsine and added arterial anastomosis. Using green fluorescence protein transgenic rats as recipients, we examined liver resident cell recruitment within graft livers by immunofluorescence costaining.
In the improved APLT model, we achieved well-regenerated grafts that could maintain regeneration for at least 4 weeks. Regarding the cell recruitment, there was no evidence of recipient-derived hepatocyte, cholangiocyte, or hepatic stellate cell recruitment into the graft. Macrophages/monocytes, however, were consistently recruited into the graft and increased over time, which might be related to inflammatory responses. Very few endothelial cells showed colocalization of markers.
We have successfully established an improved rat APLT model with arterial anastomosis as a standard technique. Using this model, we have characterized cell recruitment into the regenerating grafts.
人类辅助性部分肝移植（APLT）是一种治疗方式，尤其用于治疗儿童肝衰竭或先天性代谢疾病。APLT的动物模型有助于探索治疗方案。尽管许多研究团队提出了改进方法，但标准化手术操作一直具有挑战性。此外，移植后移植肝脏是否由受体来源的细胞重建这一问题一直存在争议。本研究的目的是改进大鼠实验性APLT并评估移植肝脏中的细胞募集情况。
为抑制受体肝脏再生并促进移植肝脏再生，我们用倒千里光碱处理受体并增加动脉吻合。以绿色荧光蛋白转基因大鼠作为受体，我们通过免疫荧光共染色检查移植肝脏内的肝驻留细胞募集情况。
在改进的APLT模型中，我们获得了再生良好的移植肝脏，其可维持再生至少4周。关于细胞募集，没有证据表明受体来源的肝细胞、胆管细胞或肝星状细胞募集到移植肝脏中。然而，巨噬细胞/单核细胞持续募集到移植肝脏中并随时间增加，这可能与炎症反应有关。极少内皮细胞显示标志物共定位。
我们成功建立了一种以动脉吻合作为标准技术的改进大鼠APLT模型。利用该模型，我们已对再生移植肝脏中的细胞募集情况进行了特征描述。
