Embryonic porcine liver as a source for transplantation: Advantage of intact liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by the quiescent host liver
Embryonic porcine liver as a source for transplantation: Advantage of intact liver implants over isolated hepatoblasts in overcoming homeostatic inhibition by the quiescent host liver
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DOI：
10.1634/stemcells.2007-0631
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发表时间：
2008-05-01
期刊：
影响因子：
5.2
通讯作者：
Reisner, Yair
中科院分区：
文献类型：
--
作者：
Katchman, Helena;Tal, Orna;Reisner, Yair
细胞治疗作为原位肝移植的替代方案是一个重大挑战，因为由于宿主肝脏表现出严格的体内平衡控制，移植后分离肝细胞的增殖可以忽略不计。因此，不同形式的肝损伤作为移植前调节的一部分是该方法的先决条件。本研究的主要目的是测试猪胎儿肝碎片异种移植是否比分离的猪胎儿肝母细胞具有更强的生长和增殖能力，在异种移植中，可能避免潜在的细胞间和细胞间的相互作用。在SCID小鼠体内移植后，与相同胎龄（胚胎28天）分离的胎儿肝母细胞相比，在静止宿主肝脏环境下，胎儿肝组织片段表现出明显的生长和增殖。免疫组织化学和形态计量学分析清楚地证明了胎猪肝碎片的增殖优势，并且不仅在植入肝脏后观察到，而且还观察到肝外部位，如脾脏和肾下被膜。所有类型的非实质肝细胞的存在对正常肝脏发育和再生至关重要。保留猪胎儿肝碎片的三维结构，可以使移植的肝细胞在静止宿主肝脏的环境下自主增殖，而不需要在移植前的条件下造成肝损伤。猪胎肝碎片具有明显的增殖和功能成熟，是一种较好的肝移植来源。
Cell therapy as an alternative to orthotopic liver transplantation represents a major challenge, since negligible proliferation of isolated hepatocytes occurs after transplantation because of the stringent homeostatic control displayed by the host liver. Thus, different modalities of liver injury as part of the pre-transplant conditioning are a prerequisite for this approach. The major objective of the present study was to test whether xenotransplantation of pig fetal liver fragments, in which potential cell-cell and cell-stroma interactions are spared, might afford more robust growth and proliferation compared with isolated pig fetal hepatoblasts. After transplantation into SCID mice, fetal liver tissue fragments exhibited marked growth and proliferation, in the setting of a quiescent host liver, compared with isolated fetal hepatoblasts harvested at the same gestational age (embryonic day 28). The proliferative advantage of fetal pig liver fragments was clearly demonstrated by immunohistochemical and morphometric assays and was observed not only after implantation into the liver but also into extrahepatic sites, such as the spleen and the subrenal capsule. The presence of all types of nonparenchymal liver cells that is crucial for normal liver development and regeneration was demonstrated in the implants. Preservation of the three-dimensional structure in pig fetal liver fragments enables autonomous proliferation of transplanted hepatic cells in the setting of a quiescent host liver, without any requirement for liver injury in the pretransplant conditioning. The marked proliferation and functional maturation exhibited by the pig fetal liver fragments suggests that it could afford a preferable source for transplantation.