Growth Ability and Repopulation Efficiency of Transplanted Hepatic Stem Cells, Progenitor Cells, and Mature Hepatocytes in Retrorsine-Treated Rat Livers
Growth Ability and Repopulation Efficiency of Transplanted Hepatic Stem Cells, Progenitor Cells, and Mature Hepatocytes in Retrorsine-Treated Rat Livers
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DOI：
10.3727/096368911x580626
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发表时间：
2012-01-01
影响因子：
3.3
通讯作者：
Mitaka, Toshihiro
中科院分区：
文献类型：
--
作者：
Ichinohe, Norihisa;Kon, Junko;Mitaka, Toshihiro
基于细胞的治疗作为肝移植的一种替代疗法已经被期待用于治疗潜在的致命性肝脏疾病。除了成熟肝细胞外，肝干/祖细胞也被认为是候选的细胞来源。然而，与mhh相比，干细胞/祖细胞是否具有移植和重新填充受体肝脏的优势尚未得到全面评估。因此，我们使用从galn处理的大鼠肝脏中分离的Thy1(+)（椭圆形）和CD44(+)（小肝细胞）细胞分别作为肝干细胞和祖细胞。将二肽基肽酶IV (DPPIV)（+）大鼠肝脏细胞移植到逆转录酶治疗的DPPIV-肝中。干细胞和祖细胞都能在宿主肝脏中分化为肝细胞。此外，直到第14天，祖细胞的生长速度都快于MHs。然而，由于祖细胞的存活时间比MHs短得多，它们的长期再生效率很低。大多数由Thy1（+）细胞产生的病灶在2个月内消失。在第60天，许多细胞在33%的cd44来源的病灶中表达衰老相关的β -半乳糖苷酶，而在13%的mh来源的病灶中观察到表达。细胞寿命短可能是由于细胞衰老所致。另一方面，与cd44来源的肝灶相比，mh来源的肝灶中窦内皮细胞融入肝灶和形成肝窦的速度更快，这可能与肝成熟有关。供体细胞的存活不仅与早期融入肝板密切相关，还与移植时细胞的分化状态密切相关。
Cell-based therapies as an alternative to liver transplantation have been anticipated for the treatment of potentially fatal liver diseases. Not only mature hepatocytes (MHs) but also hepatic stem/progenitor cells are considered as candidate cell sources. However, whether the stem/progenitor cells have an advantage to engraft and repopulate the recipient liver compared with MHs has not been comprehensively assessed. Therefore, we used Thy1(+) (oval) and CD44(+) (small hepatocytes) cells isolated from GalN-treated rat livers as hepatic stem and progenitor cells, respectively. Cells from dipeptidylpeptidase IV (DPPIV)(+) rat livers were transplanted into DPPIV- livers treated with retrorsine following partial hepatectomy. Both stem and progenitor cells could differentiate into hepatocytes in host livers. In addition, the growth of the progenitor cells was faster than that of MHs until days 14. However, their repopulation efficiency in the long term was very low, since the survival period of the progenitor cells was much shorter than that of MHs. Most foci derived from Thy1(+) cells disappeared within 2 months. Many cells expressed senescence-associated beta-galactosidase in 33% of CD44-derived foci at day 60, whereas the expression was observed in 13% of MH-derived ones. The short life of the cells may be due to their cellular senescence. On the other hand, the incorporation of sinusoidal endothelial cells into foci and sinusoid formation, which might be correlated to hepatic maturation, was completed faster in MH-derived foci than in CD44-derived ones. The survival of donor cells may have a close relation to not only early integration into hepatic plates but also the differentiated state of the cells at the time of transplantation.