Rapid clearance of transplanted hepatocytes from pulmonary capillaries in rats indicates a wide safety margin of liver repopulation and the potential of using surrogate albumin particles for safety analysis
Rapid clearance of transplanted hepatocytes from pulmonary capillaries in rats indicates a wide safety margin of liver repopulation and the potential of using surrogate albumin particles for safety analysis
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DOI：
10.1016/s0168-8278(99)80077-4
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发表时间：
1999-02-01
影响因子：
25.7
通讯作者：
Gupta, S
中科院分区：
文献类型：
--
作者：
Rajvanshi, P;Fabrega, A;Gupta, S
背景/目的：肝细胞移植肝再生的应用需要分析细胞生物分布，特别是当门脉系统分流共存时。本研究的目的是确定肝细胞移植到肺血管床的命运，并检查细胞的生物分布是否可以通过方便的替代品来近似。方法：将大鼠肝细胞和大小相近的血清大聚集体白蛋白颗粒分别注入大鼠门静脉和肺血管床，观察其生物分布、存活和功能。结果：尽管功能完好，几乎所有肝细胞在24小时内从肺毛细血管中清除，但在有或没有门静脉分流的Nagase无球蛋白血症大鼠中，血清白蛋白水平仅轻微升高，以增强门静脉因子向肺移植细胞的传递。尽管人静脉注射肝细胞接近bbb1x10(9)细胞，但血流动力学的改变仅限于右心房压的短暂性增加，肝细胞在特定血管床的分布在很大程度上由大聚集的人血清白蛋白颗粒再现。结论：肝移植过程中偶发的肺内细胞移位具有广泛的安全边际，使用大聚集血清白蛋白颗粒作为替代物进行初始短期生物分布和安全性分析将促进肝细胞移植，因为可以避免glp认证实验室的成本和稀缺供体肝脏的消耗。
Background/Aims: Applications of liver repopulation by hepatocyte transplantation require analysis of cell biodistributions, particularly when portasystemic shunting coexists. The aims of this study were to determine the fate of hepatocytes transplanted into the pulmonary vascular bed and to examine whether cell biodistributions could be approximated by convenient surrogates.Methods: Rat hepatocytes and macroaggregated serum albumin particles of similar sizes were injected into the portal and pulmonary vascular beds of rats, followed by biodistribution, survival and function analyses.Results: Although functionally intact, virtually all hepatocytes were cleared from the pulmonary capillaries within 24 h, Serum albumin levels increased minimally in Nagase analbuminemic rats with or without portacaval shunting to enhance delivery of portal factors to transplanted cells in lungs. Despite intravenous injection of hepatocytes approaching >1x10(9) cells in humans, the hemodynamic changes were limited to transient increases in right atrial pressures, The hepatocyte distributions in specific vascular beds were largely reproduced by macroaggregated human serum albumin particles.Conclusions: Incidental intrapulmonary cell translocations during liver repopulation will have a wide safety margin, Use of macroaggregated serum albumin particles as surrogates for initial short-term biodistribution and safety analysis will advance hepatocyte transplantation, as the cost of GLP-certified laboratories and consumption of scarce donor livers will be avoided.