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异种异位辅助肝移植 (XHALT) 可促进肝切除术后肝功能衰竭模型中供体肝脏的再生。

Xenogeneic Heterotopic Auxiliary Liver transplantation (XHALT) promotes native liver regeneration in a Post-Hepatectomy Liver failure model.

机构信息

Center for Transplantation Sciences, Massachusetts General Hospital/Harvard Medical School, Boston, MA, United States of America.

University of Geneva School of Medicine, Geneva, Switzerland.

出版信息

PLoS One. 2018 Nov 21;13(11):e0207272. doi: 10.1371/journal.pone.0207272. eCollection 2018.

Abstract

The liver's regenerative capacity is unique, but too small a segment can overwhelm its ability to simultaneously regenerate and support the host, resulting in liver dysfunction and death. Here we tested a temporary Xenogeneic Heterotopic Auxiliary Liver Transplant (XHALT) from Gal-KO miniature swine in a baboon model of Post-Hepatectomy Liver Failure (PHLF) by 90%- hepatectomy. Immunosuppression consisted of CVF, ATG, FK 506 and steroids. 90%-hepatectomized animals died within 4-5 days with the clinical picture of PHLF, (high LFTs and bilirubin, ascites, encephalopathy and coagulopathy). The 10% remnants had macroscopic and histological evidence of severe steatosis and absence of hepatocyte replication. In contrast, the addition of XHALT prolonged survival up to 11 days, with the cause of death being sepsis, rather than liver failure. The remnant liver appeared grossly normal, and on histology, there was no evidence of fatty infiltration, but there was pronounced Ki-67 staining. In conclusion, temporary auxiliary xenografts have the potential to support a small for size liver graft while it grows to adequate size or provide an opportunity for organ recovery in acute liver failure.

摘要

肝脏具有独特的再生能力,但如果移植的组织体积过小,可能会超过肝脏同时再生和支持宿主的能力,导致肝功能障碍和死亡。在这里,我们通过 90%肝切除术,在肝切除术后肝功能衰竭 (PHLF) 的狒狒模型中测试了来自 Gal-KO 小型猪的临时异种异位辅助肝移植 (XHALT)。免疫抑制方案由 CVF、ATG、FK506 和类固醇组成。90%肝切除的动物在 PHLF 的临床症状出现后 4-5 天内死亡,表现为高 LFTs 和胆红素、腹水、肝性脑病和凝血功能障碍。10%的剩余肝脏有严重脂肪变性的宏观和组织学证据,并且没有肝细胞复制。相比之下,添加 XHALT 将存活时间延长至 11 天,死亡原因是败血症,而不是肝功能衰竭。剩余的肝脏在大体上看起来正常,组织学上没有脂肪浸润的证据,但 Ki-67 染色明显。总之,临时辅助异种移植物有可能在小体积肝移植物生长到足够大的体积时支持其生长,或者为急性肝功能衰竭提供器官恢复的机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0c25/6248961/f4e6a3602f10/pone.0207272.g001.jpg

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