期刊
LABORATORY INVESTIGATION
卷 94, 期 6, 页码 663-673出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/labinvest.2014.55
关键词
bone tissue engineering; cell sheets; endothelial cells; osteoblasts; vascularization
资金
- Formation of Innovation Center for Fusion of Advanced Technologies in the Special Coordination Funds for Promoting Science and Technology 'Cell Sheet Tissue Engineering Center (CSTEC)'
- Global CUE program
- Multidisciplinary Education and Research Center for Regenerative Medicine (MERCREM), from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan
- Portuguese Foundation for Science and Technology (FCT) [SFRH/BD/44893/2008]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/44893/2008] Funding Source: FCT
Addressing the problem of vascularization is of vital importance when engineering three-dimensional (3D) tissues. Endothelial cells are increasingly used in tissue-engineered constructs to obtain prevascularization and to enhance in vivo neovascularization. Rat bone marrow stromal cells were cultured in thermoresponsive dishes under osteogenic conditions with human umbilical vein endothelial cells (HUVECs) to obtain honnotypic or heterotypic cell sheets (CSs). Cells were retrieved as sheets from the dishes after incubation at 20 degrees C. Monoculture osteogenic CSs were stacked on top of homotypic or heterotypic CSs, and subcutaneously implanted in the dorsal flap of nude mice for 7 days. The implants showed mineralized tissue formation under both conditions. Transplanted osteogenic cells were found at the new tissue site, demonstrating CS bone-inductive effect. Perfused vessels, positive for human CD31, confirmed the contribution of HUVECs for the neovascularization of coculture CS constructs. Furthermore, calcium quantification and expression of osteocalcin and osterix genes were higher for the CS constructs, with HUVECs demonstrating the more robust osteogenic potential of these constructs. This work demonstrates the potential of using endothelial cells, combined with osteogenic CSs, to increase the in vivo vascularization of CS-based 3D constructs for bone tissue engineering purposes.
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