Laboratory of Biomaterials and Translational Medicine, Center for Nanomedicine, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510630, China; Guangdong Provincial Key Laboratory of Liver Disease, Guangzhou, Guangdong, 510630, China.
Department of Oncology, The First Affiliated Hospital, Nanjing Medical University, Nanjing, 210029, China.
Biomaterials. 2023 Mar;294:122014. doi: 10.1016/j.biomaterials.2023.122014. Epub 2023 Jan 20.
Engineering hepatocytes as multicellular cell spheroids can improve their viability after implantation in vivo for effective rescue of the devastating acute liver failure (ALF). However, there is still a lack of straightforward methods for efficient generation of functional hepatocyte spheroids. In this study, a magnetic system, consisting of magnetic microwell arrays and magnet blocks, is developed to realize magnetically controlled 3D cell capture and spatial confinement-mediated cell aggregation. The cell spheroids with smaller size show superior hepatic functions than the larger-sized counterparts. Notably, the intrinsic magnetism of magnetic microwell arrays can regulate superoxide anions in hepatocyte spheroids and herein promote various biological processes, including antioxidation, hepatocyte-related functions, and pro-angiogenic potential. Ectopic implantation of the functional cell spheroids in ALF-challenged mice significantly prolongs the animal survival, ameliorates inflammation, and promotes liver regeneration. Hence, application of the magnetic system for generation of functionally enhanced hepatocyte spheroids holds great potential for clinical translation in the future.
工程化的肝细胞作为多细胞细胞球体，可以提高其在体内植入后的存活率，从而有效挽救毁灭性的急性肝衰竭（ALF）。然而，仍然缺乏直接有效的方法来生成功能性的肝细胞球体。在本研究中，开发了一种由磁性微井阵列和磁块组成的磁性系统，以实现磁性控制的 3D 细胞捕获和空间限制介导的细胞聚集。与较大尺寸的细胞球体相比，具有较小尺寸的细胞球体显示出更优越的肝功能。值得注意的是，磁性微井阵列的固有磁性可以调节肝细胞球体中的超氧阴离子，并促进包括抗氧化、肝细胞相关功能和促血管生成潜能在内的各种生物学过程。将功能增强的细胞球体异位植入 ALF challenged 小鼠中，可显著延长动物的存活时间，改善炎症，并促进肝再生。因此，该磁性系统在未来的临床转化中具有很大的潜力，可用于生成功能增强的肝细胞球体。
