Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells
Wholesale hepatocytic differentiation in the rat from ductular oval cells, the progeny of biliary stem cells
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DOI：
10.1016/s0168-8278(97)80051-7
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发表时间：
1997-02-01
影响因子：
25.7
通讯作者：
Sarraf, C
中科院分区：
文献类型：
--
作者：
Alison, M;Golding, M;Sarraf, C
背景/目的：当损伤后肝细胞再生受到显着阻碍时，胆道上皮细胞（导管卵圆细胞）迁移到门管周围和中区实质，卵圆细胞分化为肝细胞的潜力受到质疑。我们试图使用改良的 Solt-Farber 程序来解决这个问题，其中使用 2-乙酰氨基芴来阻断部分肝切除大鼠的肝细胞再生。方法：大鼠在三分之二肝切除术前 6 天和术后 7 天通过口服管饲法接受 2-乙酰氨基芴。通过中间丝细胞角蛋白 8 和 19 以及波形蛋白、细胞色素 P450 酶蛋白和甲胎蛋白的免疫组织化学定位来可视化细胞反应。使用反义核糖核酸探针原位观察白蛋白和甲胎蛋白 mRNA 转录物的表达。结果：在部分肝切除术后的前 9 天，长串的导管细胞从汇管区向外扩散。这些细胞表现出抗细胞角蛋白 8 和 19 抗体的强烈弥漫性细胞质染色，就像真正的胆管一样，但此外还表达波形蛋白和甲胎蛋白（蛋白质和 mRNA）——统称为“卵圆细胞表型”。此后，这些导管迅速消失，被嗜碱性肝细胞取代，嗜碱性肝细胞缺乏卵圆细胞表型，但获得了白蛋白 mRNA 的强烈表达。部分肝切除后14天，卵圆细胞表型仅限于新生汇管周围肝细胞的外周边缘、卵圆细胞导管的远端，并且这些在另外7天内也消失了。结论：在适当的实验条件下，导管卵圆细胞会分化为肝细胞。
Background/Aims: Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded, The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats.Methods: Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes.Results: During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA) - collectively termed the ''oval cell phenotype''. Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days.Conclusions: Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions.