期刊
ORGANOGENESIS
卷 10, 期 2, 页码 260-267出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/org.27590
关键词
tissue engineering; liver; fetal liver cells; vascular network; mesenchymal stem cell
资金
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [24106510, 24689052, 22390260, 21249071, 25253079]
- Research Center Network for Realization of Regenerative Medicine and the Strategic Promotion of Innovative Research and Development of the Japan Science and Technology Agency (JST) [62890004]
- Specified Research Grant of the Takeda Science Foundation
- Japan IDDM network
- Yokohama Foundation for Advanced Medical Science
- Grants-in-Aid for Scientific Research [26106721, 22390260, 23591872, 21249071, 24106510, 62890004, 25253079, 24689052] Funding Source: KAKEN
Although absolute organ shortage highlights the needs of alternative organ sources for regenerative medicine, the generation of a three-dimensional (3D) and complex vital organ, such as well-vascularized liver, remains a challenge. To this end, tissue engineering holds great promise; however, this approach is significantly limited by the failure of early vascularization in vivo after implantation. Here, we established a stable 3D in vitro pre-vascularization platform to generate human hepatic tissue after implantation in vivo. Human fetal liver cells (hFLCs) were mixed with human umbilical vein endothelial cells (HUVECs) and mesenchymal stem cells (hMSCs) and were implanted into a collagen/fibronectin matrix composite that was used as a 3-D carrier. After a couple of days, the fluorescent HUVECs developed premature vascular networks in vitro, which were stabilized by hMSCs. The establishment of functional vessels inside the pre-vascularized constructs was proven using dextran infusion studies after implantation under a transparency cranial window. Furthermore, dynamic morphological changes during embryonic liver cell maturation were intravitaly quantified with high-resolution confocal microscope analysis. The engineered human hepatic tissue demonstrated multiple liver-specific features, both structural and functional. Our new techniques discussed here can be implemented in future clinical uses and industrial uses, such as drug testing.
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