Kato K, Kasai S, Onodera K, Sawa M, Matsuda M, Kawabata N, Nakazawa F, Imai M, Kino Y, Mito M, Hodgson W J
Second Department of Surgery, Asahikawa Medical College, Japan.
Cell Transplant. 1996 Sep-Oct;5(5 Suppl 1):S27-30. doi: 10.1016/0963-6897(96)00035-8.
Fetal hepatocytes were harvested at day 20 of gestation from spontaneously hypertensive rats (SHR) and then transplanted into recipient adult SHR spleens. Morphological examination of the recipient spleens revealed that, after 4 and 10 wk, large masses of hepatocytes were present in the red pulp with apparent cord-like structures. Larger batches of hepatocytes were observed in the spleens at 10 wk after than at 4 wk after transplantation. Of major significance was the fact that hepatocyte transplanted spleens were able to express several families of cytochrome P450 (cyto P450) proteins 2-10 wk after transplantation. Immunochemical determinations revealed that cytos P450 IA1, P450 IIB1, P450 p, P450 HLp, and P450 LA omega could be detected without any prior induction. All were intensely expressed 6 wk after transplantation; however, P450 IA1 and P450 IIB1 did not appear to be expressed by 2 wk after transplantation. Although cytos P450 p and P450 HLp did not appear to be expressed by 10 wk after transplantation, they were induced with dexamethasone at that time. Cyto P450 LA omega and peroxisomal acyl CoA oxidase were expressed 6 wk after transplantation in a 70% hepatectomized host. These results demonstrate that fetal hepatocytes can be successfully transplanted into the spleens of recipients and that the fetal hepatocytes appear to grow and develop cyto P450 metabolizing systems.
在妊娠第20天从自发性高血压大鼠(SHR)获取胎儿肝细胞,然后将其移植到成年受体SHR的脾脏中。对受体脾脏进行形态学检查发现,在4周和10周后,红髓中有大量肝细胞,呈现明显的索状结构。移植后10周时在脾脏中观察到的肝细胞批次比4周时更多。具有重要意义的是,移植肝细胞的脾脏在移植后2至10周能够表达几个细胞色素P450(细胞色素P450)蛋白家族。免疫化学测定显示,无需任何预先诱导即可检测到细胞色素P450 IA1、P450 IIB1、P450 p、P450 HLp和P450 LAω。移植后6周时所有这些蛋白均强烈表达;然而,移植后2周时细胞色素P450 IA1和P450 IIB1似乎未表达。尽管细胞色素P450 p和P450 HLp在移植后10周时似乎未表达,但此时用地塞米松可诱导其表达。在70%肝切除的宿主中,移植后6周时表达细胞色素P450 LAω和过氧化物酶体酰基辅酶A氧化酶。这些结果表明,胎儿肝细胞能够成功移植到受体脾脏中,并且胎儿肝细胞似乎能够生长并发育细胞色素P450代谢系统。