球体
肝衰竭
单元格大小
细胞
化学
材料科学
生物医学工程
细胞生物学
生物物理学
纳米技术
生物
医学
内科学
生物化学
体外
作者
Jiabin Zhang,Xiaodie Chen,Yurong Chai,Chenya Zhuo,Yanteng Xu,Tiantian Xue,Dan Shao,Yu Tao,Mingqiang Li
标识
DOI:10.1002/advs.202309899
摘要
Abstract The emerging stem cell‐derived hepatocyte‐like cells (HLCs) are the alternative cell sources of hepatocytes for treatment of highly lethal acute liver failure (ALF). However, the hostile local environment and the immature cell differentiation may compromise their therapeutic efficacy. To this end, human adipose‐derived mesenchymal stromal/stem cells (hASCs) are engineered into different‐sized multicellular spheroids and co‐cultured with 3D coaxially and hexagonally patterned human umbilical vein endothelial cells (HUVECs) in a liver lobule‐like manner to enhance their hepatic differentiation efficiency. It is found that small‐sized hASC spheroids, with a diameter of ≈50 µm, show superior pro‐angiogenic effects and hepatic differentiation compared to the other counterparts. The size‐dependent functional enhancements are mediated by the Wnt signaling pathway. Meanwhile, co‐culture of hASCs with HUVECs, at a HUVECs/hASCs seeding density ratio of 2:1, distinctly promotes hepatic differentiation and vascularization both in vitro and in vivo, especially when endothelial cells are patterned into hollow hexagons. After subcutaneous implantation, the mini‐liver, consisting of HLC spheroids and 3D‐printed interconnected vasculatures, can effectively improve liver regeneration in two ALF animal models through amelioration of local oxidative stress and inflammation, reduction of liver necrosis, as well as increase of cell proliferation, thereby showing great promise for clinical translation.
科研通智能强力驱动
Strongly Powered by AbleSci AI