Department of Pathology, Immunology and Laboratory Medicine, University of Florida, College of Medicine, Gainesville, FL 32610-0275, USA.
Int J Biochem Cell Biol. 2011 Feb;43(2):214-21. doi: 10.1016/j.biocel.2010.09.005. Epub 2010 Sep 21.
Orthotopic liver transplant represent the state of the art treatment for terminal liver pathologies such as cirrhosis in adults and hemochromatosis in neonates. A limited supply of transplantable organs in relationship to the demand means that many patients will succumb to disease before an organ becomes available. One promising alternative to liver transplant is therapy based on the transplant of liver progenitor cells. These cells may be derived from the patient, expanded in vitro, and transplanted back to the diseased liver. Inborn metabolic disorders represent the most attractive target for liver progenitor cell therapy, as many of these disorders may be corrected by repopulation of only a portion of the liver by healthy cells. Another potential application for liver progenitor cell therapy is the seeding of bio-artificial liver matrix. These ex vivo bioreactors may someday be used to bridge critically ill patients to other treatments. Conferring a selective growth advantage to the progenitor cell population remains an obstacle to therapy development. Understanding the molecular signaling mechanisms and micro-environmental cues that govern liver progenitor cell phenotype may someday lead to strategies for providing this selective growth advantage. The discovery of a population of cells within the bone marrow possessing the ability to differentiate into hepatocytes may provide an easily accessible source of cells for liver therapies.
原位肝移植是治疗终末期肝脏疾病(如成人肝硬化和新生儿血色素沉着症)的最新方法。可供移植的器官数量有限,而需求却很大,这意味着许多患者在器官可用之前就会因疾病而死亡。肝祖细胞移植治疗是肝移植的一种有前途的替代方法。这些细胞可以来自患者,在体外扩增,然后再移植回病变的肝脏。先天性代谢紊乱是肝祖细胞治疗最有吸引力的目标,因为许多此类疾病可以通过健康细胞仅部分再定植来纠正。肝祖细胞治疗的另一个潜在应用是生物人工肝基质的播种。这些离体生物反应器有朝一日可能用于将重病患者过渡到其他治疗方法。为祖细胞群体赋予选择性生长优势仍然是治疗开发的障碍。了解控制肝祖细胞表型的分子信号机制和微环境线索,可能有朝一日会为提供这种选择性生长优势提供策略。骨髓中存在一群能够分化为肝细胞的细胞的发现,可能为肝治疗提供了一种易于获取的细胞来源。