(111)INDIUM LABELING OF HEPATOCYTES FOR ANALYSIS OF SHORT-TERM BIODISTRIBUTION OF TRANSPLANTED CELLS

(111)INDIUM LABELING OF HEPATOCYTES FOR ANALYSIS OF SHORT-TERM BIODISTRIBUTION OF TRANSPLANTED CELLS
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DOI:
10.1002/hep.1840190330
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发表时间:
1994-03-01
期刊:
影响因子:
13.5
通讯作者:
BHARGAVA, KK
BHARGAVA, KK
中科院分区:
医学1区
文献类型:
--
作者:
GUPTA, S;LEE, CD;BHARGAVA, KK

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肝细胞移植可用于离体基因治疗和肝脏重建。最近开发了肝重建方法,但肝细胞移植系统的优化是必要的。为了开发移植细胞生物分布的无创评估系统,我们用 (111) 铟-oxine 标记肝细胞。我们的初步研究表明,肝细胞掺入 (111)-铟-oxine 的效率约为 20%。标记后,细胞活力没有变化,并且在过夜培养后以及脾内移植后,肝细胞中存在 (111) 铟。通过闪烁成像成功地定位了移植的细胞。当肝细胞通过脾脏或颈内静脉移植时,细胞分布的闪烁扫描模式是不同的,肝细胞将细胞沉积到单独的血管床中。 (111)铟标记肝细胞生物分布的定量分析表明,在脾内移植后2小时内,细胞主要定位于肝脏和脾脏,偶尔定位于肺部。为了确定脾内细胞注射的速率是否影响肝细胞的易位,我们将细胞移植到正常大鼠体内。尽管以不同的速率进行脾内细胞注射,(111)铟标记的肝细胞的器官特异性分布保持不变。 (111)铟标记不影响移植肝细胞的长期存活。这些结果表明,肝细胞的 (111) 铟标记应极大地有助于移植肝细胞生物分布的短期无创分析。
Hepatocyte transplantation is useful for ex vivo gene therapy and liver repopulation. Methods for hepatic reconstitution have recently been developed but optimization of hepatocyte transplantation systems is necessary. To develop systems for noninvasive assessment of the biodistribution of transplanted cells, we labeled hepatocytes with (111)indium-oxine. Our initial studies showed that hepatocytes incorporated (111)-indium-oxine with an efficiency of approximately 20%. After labeling, cell viability was unchanged and (111)indium was present in hepatocytes after overnight culture, as well as after intrasplenic transplantation. Transplanted cells were successfully localized by means of scintigraphic imaging. The scintigraphic patterns of cell distribution were different when hepatocytes were transplanted by means of either spleen or internal jugular vein, which deposit cells into separate vascular beds. Quantitative analysis of the biodistribution of (111)indium-labeled hepatocytes indicated that within 2 hr of intrasplenic transplantation, cells were predominantly localized in liver and spleen, and occasionally in lungs. To determine whether the rate of intrasplenic cell injection influenced translocation of hepatocytes, we transplanted cells in normal rats. Despite intrasplenic cell injection at a variety of rates, organ-specific distribution of (111)indium-labeled hepatocytes remained unchanged. Labeling with (111)indium did not affect long-term survival of transplanted hepatocytes. These results indicate that (111)indium-labeling of hepatocytes should greatly assist noninvasive analysis in the short-term of the biodistribution of transplanted hepatocytes.