Center for Engineering in Medicine, Massachusetts General Hospital, Harvard Medical School, and the Shriners Hospitals for Children, 51 Blossom Street, Boston, MA 02114, USA.
Nat Rev Gastroenterol Hepatol. 2012 Dec;9(12):738-44. doi: 10.1038/nrgastro.2012.140. Epub 2012 Aug 14.
Initially hailed as the ultimate solution to organ failure, engineering of vascularized tissues such as the liver has stalled because of the need for a well-structured circulatory system that can maintain the cells seeded inside the construct. A new approach has evolved to overcome this obstacle. Whole-organ decellularization is a method that retains most of the native vascular structures of the organ, providing microcirculatory support and structure, which can be anastomosed with the recipient circulation. The technique was first applied to the heart and then adapted for the liver. Several studies have shown that cells can be eliminated, the extracellular matrix and vasculature are reasonably preserved and, after repopulation with hepatocytes, these grafts can perform hepatic functions in vitro and in vivo. Progress is rapidly being made as researchers are addressing several key challenges to whole-organ tissue engineering, such as ensuring correct cell distribution, nonparenchymal cell seeding, blood compatibility, immunological concerns, and the source of cells and matrices.
最初,工程化血管化组织(如肝脏)被吹捧为解决器官衰竭的终极方案,但由于需要一个结构良好的循环系统来维持构建体内部的细胞,该技术的发展陷入了停滞。为了克服这一障碍,出现了一种新的方法。整个器官去细胞化是一种保留器官大部分固有血管结构的方法,为细胞提供了微循环支持和结构,这些结构可以与受体循环吻合。该技术最初应用于心脏,然后适用于肝脏。多项研究表明,可以消除细胞,合理保留细胞外基质和脉管系统,并且在用肝细胞再种植后,这些移植物可以在体外和体内发挥肝脏功能。随着研究人员解决整个器官组织工程的几个关键挑战,如确保正确的细胞分布、非实质细胞接种、血液相容性、免疫问题以及细胞和基质的来源,该技术正在迅速发展。