Flohr Tanya R, Bonatti Hugo, Brayman Kenneth L, Pruett Timothy L
Department of Surgery, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA.
Curr Opin Organ Transplant. 2009 Feb;14(1):64-71. doi: 10.1097/MOT.0b013e328320fd7b.
Cell transplantation to restore liver function as an alternative to whole liver transplantation has thus far not been successful in humans.
Adult mature hepatocytes and various populations of liver progenitors and stem cells are being studied for their regenerative capabilities. Hepatocyte transplantation to treat metabolic deficiencies has shown promising early improvement in liver function; however, long-term success has not been achieved. Liver progenitor cells can now be identified and were shown to be capable to differentiate into a hepatocyte-like phenotype. Despite evidence of mesenchymal stem cell fusion in animal models of liver regeneration, encouraging results were seen in a small group of patients receiving autologous transplantation of CD133 mesenchymal stem cells to repopulate the liver after extensive hepatectomy for liver masses. Ethical issues, availability, potential rejection and limited understanding of the totipotent capabilities of embryonic stem cells are the limitations that prevent their use for restoration of liver function. The effectiveness of embryonic stem cells to support liver function has been proven with their application in the bioartificial liver model in rodents.
There is ongoing research to restore liver function in cell biology, animal models and clinical trials using mature hepatocytes, liver progenitor cells, mesenchymal stem cells and embryonic stem cells.
细胞移植作为全肝移植的替代方法来恢复肝功能,目前在人类中尚未取得成功。
正在研究成年成熟肝细胞以及各种肝祖细胞和干细胞群体的再生能力。肝细胞移植治疗代谢缺陷已显示出早期肝功能有令人鼓舞的改善;然而,尚未取得长期成功。现在可以识别肝祖细胞,并且已证明它们能够分化为肝细胞样表型。尽管在肝再生动物模型中有间充质干细胞融合的证据,但在一小部分接受CD133间充质干细胞自体移植以在因肝肿块进行广泛肝切除术后重建肝脏的患者中看到了令人鼓舞的结果。伦理问题、可用性、潜在排斥以及对胚胎干细胞全能能力的了解有限是阻碍其用于恢复肝功能的限制因素。胚胎干细胞在啮齿动物生物人工肝模型中的应用已证明其支持肝功能的有效性。
目前正在进行利用成熟肝细胞、肝祖细胞、间充质干细胞和胚胎干细胞在细胞生物学、动物模型和临床试验中恢复肝功能的研究。