期刊
BIOMATERIALS
卷 34, 期 8, 页码 1878-1887出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2012.09.024
关键词
Stem cell; Emergent behavior; Tissue; Phenotype; Biomimetic material; Tissue engineering
资金
- Alexander von Humboldt Foundation
- National Science Foundation [CMMI-0826435]
- AO Foundation
- Spanish Ministry of Science and Innovation (MICINN) [RYC2009-04275, MAT2008-04192]
- Department of Industry of the Basque Government
- INSERM ATIP-AVENIR program
- Marie Curie IRG programs
- Gene Expression and Genotyping Core Facility of the Case Comprehensive Cancer Center [NIH P30 CA43703]
A challenge to mimicking nature's bottom up approach to generate tissue is the coordination of cellular self-assembly and emergent phenotype. Here we create a biosynthetic platform to mimic native cell cell interactions and to drive emergent tissue behavior by human multipotent cells from the periosteal niche, i.e. PDCs, whose regenerative capacity is equal or greater to those from the bone marrow niche. Western blots showed that human PDCs express proteins for both N-cadherin, a hallmark of mesenchymal condensation, as well as for ZO-1, a tight junction membrane protein conferring epithelial barrier membrane properties. Hence, we functionalized a solid supported lipid bilayer (SLB) membrane with recombinant N-cadherin and investigated the short term phenotype of PDCs seeded on unfunctionalized and N-cadherin functionalized SLBs compared to that of PDCs seeded on glass coverslips. After 24 h, SLB functionalization promoted aggregation of PDCs seeded at high density (35,000 cells/cm(2)), with no significant concomitant changes in transcription of N-cadherin (CDH2) as measured by rtPCR. In contrast, cells seeded on unfunctionalized SLBs remained non-adherent but showed a significant upregulation in transcription of N-cadherin. Furthermore, culture of PDCs at high density on N-cadherin functionalized SLBs was negatively correlated with expression of ZO-1, while culture on unfunctionalized SLBs was positively correlated with the expression of the tight junction membrane protein. High density seeding on N-cadherin functionalized and unfunctionalized SLBs places PDCs in distinct cellular contexts and relates to emergent behavior typical for mesenchymal condensation. These studies demonstrate a biosynthetic in vitro cell culture platform to elucidate and guide emergent tissue architectures by PDCs. (C) 2012 Elsevier Ltd. All rights reserved.
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