Li Kewei, Tharwat Mohammad, Larson Ellen L, Felgendreff Philipp, Hosseiniasl Seyed M, Rmilah Anan Abu, Safwat Khaled, Ross Jeffrey J, Nyberg Scott L
Department of Surgery, Mayo Clinic, Rochester, MN, United States.
Department of Pediatric Surgery, West China Hospital of Sichuan University, Chengdu, China.
Front Bioeng Biotechnol. 2022 Mar 10;10:833163. doi: 10.3389/fbioe.2022.833163. eCollection 2022.
Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs. For example, vascular patency and appropriate cell distribution and expansion are critical components in the production of successful BELs. Proper solutions to these components of BELs have challenged its development. Several strategies, such as heparin immobilization, heparin-gelatin, REDV peptide, and anti-CD31 aptamer have been developed to extend the vascular patency of revascularized bioengineered livers (rBELs). Other novel methods have been developed to enhance cell seeding of parenchymal cells and to increase graft functionality during both bench and perfusion. These enhanced methods have been associated with up to 15 days of survival in large animal (porcine) models of heterotopic transplantation but have not yet permitted extended survival after implantation of BELs in the orthotopic position. This review will highlight both the remaining challenges and the potential for clinical application of functional bioengineered grafts.
生物工程肝脏(BELs)是解决肝脏移植供体器官短缺问题的一种有吸引力的治疗选择。BELs技术的目标是替代或再生天然人类肝脏。已经提出了多种用于可移植肝脏组织工程的方法;本综述将重点介绍BELs的去细胞化-再细胞化方法。例如,血管通畅以及适当的细胞分布和增殖是成功生产BELs的关键组成部分。解决BELs这些组成部分的适当方法对其发展构成了挑战。已经开发了几种策略,如肝素固定、肝素-明胶、REDV肽和抗CD31适体,以延长血管化生物工程肝脏(rBELs)的血管通畅性。还开发了其他新方法来增强实质细胞的细胞接种,并在实验台和灌注过程中提高移植物功能。这些改进方法在大型动物(猪)异位移植模型中已实现长达15天的存活,但在将BELs原位植入后尚未实现延长存活。本综述将重点介绍功能性生物工程移植物在临床应用中仍然存在的挑战和潜力。