Gupta S, Yerneni P R, Vemuru R P, Lee C D, Yellin E L, Bhargava K K
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461.
Hum Gene Ther. 1993 Jun;4(3):249-57. doi: 10.1089/hum.1993.4.3-249.
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 111Indium-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.
移植到宿主肝脏的肝细胞能迅速植入，保持正常功能，并能无限期存活。尽管脾内移植能有效地将肝细胞输送到肝脏，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。在正常大鼠中，肝细胞移植后门静脉压力增加了几倍，但在3周内恢复正常。相比之下，在部分门静脉结扎或肝硬化的门静脉高压大鼠中，肝细胞移植后门静脉压力要么没有变化，要么升高较少。然而，在门静脉高压大鼠中，随着右心房压力的升高，更多的移植细胞迁移到肺部。使用铟-111标记的肝细胞进行的进一步定量研究表明，所有动物组中移植肝细胞的脾内滞留情况相似。正常大鼠和肝硬化大鼠的肝内细胞移位情况相当，而在部分门静脉结扎大鼠中，迁移到肝脏的细胞较少。然而，最显著的差异是门静脉高压大鼠中肝细胞的肺内移位明显增加，这可能与门体分流有关。这些结果表明，由于脾内肝细胞移植在正常受试者中仅诱导短暂的门静脉高压，增加肝脏再植的潜在策略可能包括重复细胞移植。这对于优化体外基因治疗或其他基于肝细胞的治疗结果应该是有用的。然而，如果要避免严重并发症，门静脉高压或肝硬化受试者的肝脏和门静脉血流动力学状态需要仔细评估。
