Grompe M
Department of Molecular and Medical Genetics, Department of Pediatrics, Oregon Health Sciences University, Portland 97201, USA.
J Inherit Metab Dis. 2001 Apr;24(2):231-44. doi: 10.1023/a:1010375203539.
Orthotopic liver transplantation is the treatment of choice for several inborn errors of metabolism. Unfortunately, the supply of donor organs is limiting and therefore many patients cannot benefit from this therapy. In contrast, hepatocyte transplantation could potentially overcome the shortage in donor livers by use of cells from a single donor for multiple recipients. In classic hepatocyte transplantation, however, only 1% of the liver mass or less can be replaced by donor cells. Recently, though, it has been shown in animal models that >90% of host hepatocytes can be replaced by a small number of transplanted donor cells in a process we term 'therapeutic liver repopulation'. This phenomenon is analogous to repopulation of the haematopoietic system after bone marrow transplantation. Liver repopulation occurs when transplanted cells have a growth advantage in the setting of damage to recipient liver cells. It has been discovered that transplanted cells from extrahepatic sources such as the adult pancreas or bone marrow can also be used for liver repopulation. Because bone marrow donors are widely available, this finding raises the hope of therapeutic application of these cells in the future. Here, the current knowledge regarding therapeutic liver repopulation and the hopeful implications for treatment of liver diseases will be discussed.
原位肝移植是治疗多种先天性代谢缺陷的首选方法。不幸的是，供体器官的供应有限，因此许多患者无法从这种治疗中受益。相比之下，肝细胞移植有可能通过将来自单个供体的细胞用于多个受体来克服供体肝脏的短缺。然而，在经典的肝细胞移植中，供体细胞只能替代1%或更少的肝脏质量。不过，最近在动物模型中发现，在我们称之为“治疗性肝脏再填充”的过程中，少量移植的供体细胞可以替代超过90%的宿主肝细胞。这种现象类似于骨髓移植后造血系统的再填充。当移植细胞在受体肝细胞受损的情况下具有生长优势时，就会发生肝脏再填充。已经发现，来自肝外来源（如成人胰腺或骨髓）移植的细胞也可用于肝脏再填充。由于骨髓供体广泛可得，这一发现为这些细胞在未来的治疗应用带来了希望。在此，将讨论关于治疗性肝脏再填充的当前知识以及对肝脏疾病治疗的潜在意义。
