STUDIES ON THE SAFETY OF INTRASPLENIC HEPATOCYTE TRANSPLANTATION - RELEVANCE TO EXVIVO GENE-THERAPY AND LIVER REPOPULATION IN ACUTE HEPATIC-FAILURE
STUDIES ON THE SAFETY OF INTRASPLENIC HEPATOCYTE TRANSPLANTATION - RELEVANCE TO EXVIVO GENE-THERAPY AND LIVER REPOPULATION IN ACUTE HEPATIC-FAILURE
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DOI：
10.1089/hum.1993.4.3-249
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发表时间：
1993-06-01
影响因子：
4.2
通讯作者：
BHARGAVA, KK
中科院分区：
文献类型：
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作者：
GUPTA, S;YERNENI, PR;BHARGAVA, KK
移植到宿主肝脏中的肝细胞能迅速移植，保持正常功能，并能无限期存活。尽管脾内移植在将肝细胞运送到肝脏方面是有效的，但为了确定潜在的限制性并发症，我们研究了其在正常、肝硬化和部分门静脉结扎大鼠中的安全性。正常大鼠肝细胞移植后门静脉压力增加数倍，但在3周内恢复正常。相比之下，在门静脉部分结扎或肝硬化的门脉高压大鼠中，肝细胞移植后门静脉压力不变或增加较少。然而，随着门脉高压大鼠右心房压力的升高，更多的移植细胞迁移到肺部。进一步使用铟111标记的肝细胞进行定量研究表明，移植肝细胞的脾内滞留在所有动物组中都是相似的。正常大鼠和肝硬化大鼠的肝内细胞移位相似，而部分门静脉结扎大鼠的肝内细胞迁移较少。然而，最显著的差异是门脉高压大鼠肝细胞肺内移位明显增加，这可能与门脉系统分流有关。这些结果表明，由于脾内肝细胞移植在正常受试者中只引起暂时的门静脉高压症，增加肝脏再生的潜在策略可能包括重复的细胞移植。这将有助于优化体外基因治疗的结果，或其他基于肝细胞的治疗。然而，如果要避免严重的并发症，门脉高压或肝硬化患者的肝脏和门脉血流动力学状况需要仔细评估。
Hepatocytes transplanted into the host liver engraft promptly, retain normal function, and survive indefinitely. Although intrasplenic transplantation is effective in delivering hepatocytes to the liver, to define potentially limiting complications, we studied its safety in normal, cirrhotic, and partial portal vein-ligated rats. In normal rats, portal pressures increased severalfold after hepatocyte transplantation but returned to normal within 3 weeks. In contrast, in portal hypertensive rats with partial portal vein ligation or cirrhosis, portal pressures were either unchanged or increased less after hepatocyte transplantation. However, more transplanted cells migrated to the lungs along with a rise in right atrial pressures in portal hypertensive rats. Further quantitative studies using Indium-111-labeled hepatocytes showed that intrasplenic retention of transplanted hepatocytes was similar in all animal groups. Intrahepatic cell translocation was comparable in normal and cirrhotic rats, whereas fewer cells migrated to the liver in partial portal vein-ligated rats. The most remarkable difference, however, was significantly greater intrapulmonary translocation of hepatocytes in portal hypertensive rats, which was presumably related to portosystemic shunting. These results indicate that because intrasplenic hepatocyte transplantation induces only temporary portal hypertension in normal subjects, potential strategies to augment liver repopulation could include repeated cell transplantation. This should be useful for optimizing the results of ex vivo gene therapy, or other hepatocyte-based therapies. However, the hepatic and portal hemodynamic status requires careful evaluation in portal hypertensive or cirrhotic subjects if serious complications are to be avoided.