部分肝切除术后支持性肝细胞移植增强临床前猪模型的肝再生。

Supportive Hepatocyte Transplantation after Partial Hepatectomy Enhances Liver Regeneration in a Preclinical Pig Model.

机构信息

ReMediES, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany,

ReMediES, Department of General, Visceral and Transplant Surgery, Hannover Medical School, Hannover, Germany.

出版信息

Eur Surg Res. 2021;62(4):238-247. doi: 10.1159/000516690. Epub 2021 May 27.

DOI:10.1159/000516690

PMID:34044396

Abstract

BACKGROUND

Hepatocyte transplantation (HTx) is regarded as a potential treatment modality for various liver diseases including acute liver failure. We developed a preclinical pig model to evaluate if HTx could safely support recovery from liver function impairment after partial hepatectomy.

METHODS

Pigs underwent partial hepatectomy with reduction of the liver volume by 50% to induce a transient but significant impairment of liver function. Thereafter, 2 protocols for HTx were evaluated and compared to a control group receiving liver resection only (group 1, n = 5). Portal pressure-controlled HTx was performed either immediately after surgery (group 2, n = 6) or 3 days postoperatively (group 3, n = 5). In all cases, liver regeneration was monitored by conventional laboratory tests and the novel noninvasive maximum liver function capacity (LiMAx) test with a follow-up of 4 weeks.

RESULTS

Partial hepatectomy significantly impaired liver function according to conventional liver function tests as well as LiMAx in all groups. A mean of 4.10 ± 1.1 × 108 and 3.82 ± 0.7 × 108 hepatocytes were transplanted in groups 2 and 3, respectively. All animals remained stable with respect to vital parameters during and after HTx. The animals in group 2 showed enhanced liver regeneration as observed by mean postoperative LiMAx values (621.5 vs. 331.3 μg/kg/h on postoperative day 7; p < 0.001) whereas HTx in group 3 led to a significant increase in mean liver-specific coagulation factor VII (112.2 vs. 54.0% on postoperative day 7; p = 0.003) compared to controls (group 1), respectively. In both experimental groups, thrombotic material was observed in the portal veins and pulmonary arteries on histology, despite the absence of clinical symptoms.

CONCLUSION

HTx can be performed safely and effectively immediately after a partial (50%) hepatectomy as well as 3 days postoperatively, with comparable results regarding the enhancement of liver function and regeneration.

摘要

背景

肝细胞移植（HTx）被认为是治疗各种肝脏疾病的一种潜在治疗方法，包括急性肝功能衰竭。我们开发了一种临床前猪模型，以评估 HTx 是否可以安全地支持部分肝切除术后肝功能恢复。

方法

猪接受部分肝切除术，肝体积减少 50%，以导致肝功能短暂但显著受损。此后，评估了两种 HTx 方案，并与仅接受肝切除术的对照组进行比较（第 1 组，n=5）。门静脉压控 HTx 分别在手术后立即进行（第 2 组，n=6）或术后 3 天进行（第 3 组，n=5）。在所有情况下，通过常规实验室检查和新型非侵入性最大肝功能容量（LiMAx）试验监测肝再生，并随访 4 周。

结果

部分肝切除术使所有组的肝功能均根据常规肝功能试验和 LiMAx 显著受损。第 2 组和第 3 组分别移植了平均 4.10±1.1×108 和 3.82±0.7×108 个肝细胞。所有动物在 HTx 期间和之后的生命参数均保持稳定。第 2 组的动物显示出增强的肝再生，表现为术后第 7 天平均 LiMAx 值增加（621.5 对 331.3μg/kg/h；p<0.001），而第 3 组的 HTx 导致平均肝特异性凝血因子 VII 显著增加（112.2%对 54.0%；p=0.003）与对照组（第 1 组）相比。在这两个实验组中，尽管没有临床症状，但组织学上仍观察到门静脉和肺动脉中的血栓形成物质。