title: Fabrication of Biomimetic Bone Tissue Using Mesenchymal Stem Cell-Derived Three-Dimensional Constructs Incorporating Endothelial Cells.
abstract: The development of technologies to promote vascularization of engineered tissue would drive major developments in tissue engineering and regenerative medicine. Recently, we succeeded in fabricating three-dimensional (3D) cell constructs composed of mesenchymal stem cells (MSCs). However, the majority of cells within the constructs underwent necrosis due to a lack of nutrients and oxygen. We hypothesized that incorporation of vascular endothelial cells would improve the cell survival rate and aid in the fabrication of biomimetic bone tissues in vitro. The purpose of this study was to assess the impact of endothelial cells combined with the MSC constructs (MSC/HUVEC constructs) during short- and long-term culture. When human umbilical vein endothelial cells (HUVECs) were incorporated into the cell constructs, cell viability and growth factor production were increased after 7 days. Furthermore, HUVECs were observed to proliferate and self-organize into reticulate porous structures by interacting with the MSCs. After long-term culture, MSC/HUVEC constructs formed abundant mineralized matrices compared with those composed of MSCs alone. Transmission electron microscopy and qualitative analysis revealed that the mineralized matrices comprised porous cancellous bone-like tissues. These results demonstrate that highly biomimetic bone tissue can be fabricated in vitro by 3D MSC constructs incorporated with HUVECs.
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Sasaki
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hashimoto
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamaguchi
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan; Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Itsumi
authors.initials: I
authors.lastname: Yoshimoto
authors.affiliation: Department of Biomaterials, Okayama University, Okayama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsumoto
authors.affiliation: Department of Biomaterials Science, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imazato
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry; D001842:Bone and Bones / Q000166:cytology / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D008903:Minerals / Q000378:metabolism; D010012:Osteogenesis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D008903:Minerals; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D000469:Alkaline Phosphatase