The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes
The origin of biliary ductular cells that appear in the spleen after transplantation of hepatocytes
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DOI：
10.3727/000000004772664860
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
Terada, N
中科院分区：
文献类型：
--
作者：
Fukuda, K;Sugihara, A;Terada, N
将大鼠肝细胞移植到同系大鼠脾脏中导致细胞角蛋白（CK）-19阳性胆管细胞形成小管。CK-19阳性细胞的确切来源尚不清楚，它们可能来源于移植肝细胞制剂中的胆管细胞或卵圆细胞前体。在本研究中，我们发现，CK-19阳性细胞的数量迅速增加后，肝细胞移植，4周时达到最高，然后逐渐下降。然而，CK-19阳性胆管细胞的Ki-67标记指数较低，在整个实验期间没有显着变化。此外，没有或很少CK-19阳性细胞出现在脾移植后的非实质肝细胞富集胆管细胞。这些结果表明，胆汁细胞不是脾脏中CK-19阳性细胞的来源。在肝细胞移植前24小时给予4，4 '-二氨基二苯基甲烷，损害肝脏中卵圆细胞的前体细胞，但不能阻止脾脏中CK-19阳性胆汁细胞的出现。此外，移植的非实质细胞携带的卵圆细胞的数量增加，通过治疗与2-乙酰氨基芴和部分肝切除术导致没有出现CK-19阳性的胆汁细胞在脾脏中。这些结果排除了卵圆细胞作为脾脏中CK-19阳性胆管细胞的来源。由于CK-19阳性胆管细胞出现在脾脏中，只有肝细胞组分移植，我们建议肝细胞的转分化可能是CK-19阳性胆管细胞产生的机制。
Transplantation of rat hepatocytes into the syngeneic rat spleen results in the appearance of cytokeration (CK)-19-positive biliary cells that form ductules. The exact origin of CK-19-positive cells is not known and the possibility that they are derived from biliary cells or precursors of oval cells in transplanted hepatocyte preparations has been raised. In the present study, we found that the number of CK-19-positive biliary cells increased rapidly after transplantation of hepatocytes, reached the maximum at 4 weeks, and then gradually decreased. However, a Ki-67 labeling index of CK-19-positive biliary cells was low and showed no significant changes throughout the experimental period. In addition, no or few CK-19-positive cells appeared in the spleen after transplantation of nonparenchymal liver cells enriched with biliary cells. These results showed that biliary cells were not the source of CK-19-positive cells in the spleen. Impairment of precursors of oval cells in the liver by administration of 4,4'-diaminodiphenylmethane 24 h before transplantation of hepatocytes did not prevent the appearance of CK-19-positive biliary cells in the spleen. Moreover, transplantation of nonparenchymal cells carrying an increased number of oval cells by means of treatment with 2-acetylamino-fluorene and partial hepatectomy resulted in no appearance of CK-19-positive biliary cells in the spleen. These results ruled out oval cells as the origin of CK-19-positive biliary cells in the spleen. Because CK-19-positive biliary cells appeared in the spleen only when hepatocyte fractions were transplanted, we suggest transdifferentiation of heptocytes may be the mechanism by which CK-19-positive biliary cells are generated.