Wake Forest Institute for Regenerative Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27101, USA.
World J Gastroenterol. 2012 Dec 21;18(47):6926-34. doi: 10.3748/wjg.v18.i47.6926.
The present review aims to illustrate the strategies that are being implemented to regenerate or bioengineer livers for clinical purposes. There are two general pathways to liver bioengineering and regeneration. The first consists of creating a supporting scaffold, either synthetically or by decellularization of human or animal organs, and seeding cells on the scaffold, where they will mature either in bioreactors or in vivo. This strategy seems to offer the quickest route to clinical translation, as demonstrated by the development of liver organoids from rodent livers which were repopulated with organ specific cells of animal and/or human origin. Liver bioengineering has potential for transplantation and for toxicity testing during preclinical drug development. The second possibility is to induce liver regeneration of dead or resected tissue by manipulating cell pathways. In fact, it is well known that the liver has peculiar regenerative potential which allows hepatocyte hyperplasia after amputation of liver volume. Infusion of autologous bone marrow cells, which aids in liver regeneration, into patients was shown to be safe and to improve their clinical condition, but the specific cells responsible for liver regeneration have not yet been determined and the underlying mechanisms remain largely unknown. A complete understanding of the cell pathways and dynamics and of the functioning of liver stem cell niche is necessary for the clinical translation of regenerative medicine strategies. As well, it will be crucial to elucidate the mechanisms through which cells interact with the extracellular matrix, and how this latter supports and drives cell fate.
本综述旨在说明为临床目的而进行肝脏再生或生物工程的策略。肝脏生物工程和再生有两种一般途径。第一种方法是创建支持支架，无论是通过合成还是通过人类或动物器官的去细胞化，然后在支架上接种细胞，使它们在生物反应器或体内成熟。正如从啮齿动物肝脏中生成具有器官特异性的动物和/或人类来源细胞的肝类器官的发展所表明的那样，这种策略似乎为临床转化提供了最快的途径。肝脏生物工程具有移植和临床前药物开发期间毒性测试的潜力。第二种可能性是通过操纵细胞途径诱导死亡或切除组织的肝脏再生。事实上，众所周知，肝脏具有特殊的再生潜力，允许在肝脏体积切除后肝细胞增生。将有助于肝脏再生的自体骨髓细胞输注到患者中已被证明是安全的，并改善了他们的临床状况，但尚未确定负责肝脏再生的确切细胞，其潜在机制在很大程度上仍然未知。为了将再生医学策略转化为临床应用，需要充分了解细胞途径和动态以及肝干细胞龛的功能。阐明细胞与细胞外基质相互作用的机制以及细胞外基质如何支持和驱动细胞命运也至关重要。
