Gunsalus J R, Brady D A, Coulter S M, Gray B M, Edge A S
Department of Molecular and Cellular Biology, Diacrin Inc., Charlestown, Massachusetts 02129, USA.
Nat Med. 1997 Jan;3(1):48-53. doi: 10.1038/nm0197-48.
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 Watanable heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous familial hypercholesterolemia, and 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.
异种肝细胞移植将为肝脏疾病提供一种新的治疗方法，并有助于解决供体器官供应不足的问题。我们已经测试了注入肝脏的异种细胞是否能纠正Watanable遗传性高脂血症（WHHL）兔的代谢缺陷，WHHL兔是纯合子家族性高胆固醇血症的动物模型，并且我们已经研究了注入的细胞是否穿过门静脉血管的内膜。我们发现，猪肝细胞在手术后定位于肝血窦，随后从血管中迁移出来并整合到肝实质中。整合后的猪肝细胞提供功能性低密度脂蛋白受体，可使WHHL兔的血清胆固醇至少在100天内降低30%-60%。
