Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation
Reduction of serum cholesterol in Watanabe rabbits by xenogeneic hepatocellular transplantation
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DOI：
10.1038/nm0197-48
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发表时间：
1997-01-01
期刊：
影响因子：
82.9
通讯作者：
Edge, ASB
中科院分区：
文献类型：
--
作者：
Gunsalus, JR;Brady, DA;Edge, ASB
异种肝细胞移植为肝脏疾病的治疗提供了一种新的方法，并将有助于解决供体器官供应不足的问题。我们已经测试了异种细胞注入肝脏是否可以纠正Watanabe遗传性高胆固醇血症（WHHL）兔（纯合子家族性高胆固醇血症的动物模型）的代谢缺陷，兰德我们已经研究了注入的细胞是否穿过门静脉血管的衬里。我们发现，猪肝细胞在手术后定位于肝窦，随后迁移出血管并整合到肝实质中。整合的猪肝细胞提供了功能性LDL受体，可在至少100天内将WHHL兔的血清胆固醇降低30-60%。
Transplantation of xenogeneic hepatocytes would provide a novel therapy for liver disease and would help to solve the problem of an insufficient supply of donor organs. We have tested whether xenogeneic cells infused into the liver could correct the metabolic defect in the Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous familial hypercholesterolemia, rand we have investigated whether the infused cells traverse the lining of the portal vasculature. We find that porcine hepatocytes are localized in the hepatic sinusoids after surgery and subsequently migrate out of the vessels and integrate into the hepatic parenchyma. The integrated porcine hepatocytes provide functional LDL receptors that lower serum cholesterol in the WHHL rabbit by 30-60% for at least 100 days.