title: Decellularized extracellular matrix of human umbilical vein endothelial cells promotes endothelial differentiation of stem cells from exfoliated deciduous teeth.
abstract: Dental stem cells can serve as a potential source of functional endothelial cells for tissue engineering applications, but the endothelial-lineage differentiation efficiency is rather low even with growth factors and mechanical stimuli, which greatly limits their clinical applications. This is partly due to the deficiency of standard two-dimensional (2-D) culture systems, which is unable to recapitulate the three-dimensional (3-D) in vivo milieu that is rich in extracellular matrix. Hence, we extracted decellularized extracellular matrix from human umbilical vein endothelial cells (HUVECs-DECM) to provide a bioactive substratum conducive to the endothelial differentiation of dental stem cells. Compared to cells plated on tissue culture polystyrene (TCP), stem cells from exfoliated deciduous teeth (SHED) cultured on the HUVECs-DECM demonstrated more regular arrangement and elongated morphology. HUVECs-DECM significantly enhanced the rapid adhesion and proliferation rates of SHED, as demonstrated by WST-8 assay and immunocytochemistry indicating higher expression levels of vinculin by newly adherent SHED on HUVECs-DECM versus TCP. In addition, there was twofold to fivefold higher mRNA expression levels of endothelial-specific markers CD31 and VEGFR-2 in SHED after seven days of culture on DECM versus TCP. Functional testing with in vitro matrigel angiogenesis assay identified more capillary-like structure formation with significantly higher tubule length in SHED induced by DECM versus TCP. Hence, the results of this study provide a better understanding of the unique characteristics of cell-specific ECM and demonstrated the potential use of HUVECs-DECM as a culture substratum conducive for stimulating the endothelial differentiation of SHED for therapeutic angiogenic applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1083-1093, 2017.
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Gong
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.|Department of Biological Sciences, Sunway University, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
authors.forename: Boon Chin
authors.initials: BC
authors.lastname: Heng
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Shaoyue
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Changyong
authors.initials: C
authors.lastname: Yuan
authors.affiliation: Department of Dental Public Health, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.
authors.forename: Edward Chin Man
authors.initials: EC
authors.lastname: Lo
authors.affiliation: Department of Endodontology, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong, China.|HKU Shenzhen Institute of Research and Innovation, Hong Kong, China.
authors.forename: Chengfei
authors.initials: C
authors.lastname: Zhang
mesh_terms: D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000737:chemistry*; D061307:Human Umbilical Vein Endothelial Cells / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D006801:Humans; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014094:Tooth, Deciduous / Q000166:cytology / Q000378:metabolism
keywords: angiogenesis; decellularization; dental pulp stem cells; endothelial cells; extracellular matrix; tissue engineering