title: Transplantation of three-dimensional artificial human vascular tissues fabricated using an extracellular matrix nanofilm-based cell-accumulation technique.
abstract: We have established a novel three-dimensional (3D) tissue-constructing technique, referred to as the 'cell-accumulation method', which is based on the self-assembly of cultured human cells. In this technique, cells are coated with fibronectin and gelatin to construct extracellular matrix (ECM) nanofilms and cultured to form multi-layers in vitro. By using this method, we have successfully fabricated artificial tissues with vascular networks constructed by co-cultivation of human umbilical vein-derived vascular endothelial cells between multi-layers of normal human dermal fibroblasts. In this study, to assess these engineered vascular tissues as therapeutic implants, we transplanted the 3D human tissues with microvascular networks, fabricated based on the cell-accumulation method, onto the back skin of nude mice. After the transplantation, we found vascular networks with perfusion of blood in the transplanted graft. At the boundary between host and implanted tissue, connectivity between murine and human vessels was found. Transmission electron microscopy of the implanted artificial vascular tubules demonstrated the ultrastructural features of blood capillaries. Moreover, maturation of the vascular tissues after transplantation was shown by the presence of pericyte-like cells and abundant collagen fibrils in the ECM surrounding the vasculature. These results demonstrated that artificial human vascular tissues constructed by our method were engrafted and matured in animal skin. In addition, the implanted artificial human vascular networks were connected with the host circulatory system by anastomosis. This method is an attractive technique for engineering prevascularized artificial tissues for transplantation. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Neuroanatomy, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Japan.
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Asano
authors.affiliation: Department of Neuroanatomy, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Japan.|Department of Anatomical Science, Hirosaki University Graduate School of Medicine, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shimoda
authors.affiliation: Department of Neuroanatomy, Cell Biology and Histology, Hirosaki University Graduate School of Medicine, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Okano
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Japan.
authors.forename: Michiya
authors.initials: M
authors.lastname: Matsusaki
authors.affiliation: Department of Applied Chemistry, Graduate School of Engineering, Osaka University, Japan.
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D001187:Artificial Organs; D001808:Blood Vessels / Q000637:transplantation* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D023822:Tissue Engineering / Q000379:methods*
keywords: blood vessels; cell-accumulation technique; electron microscopy; extracellular matrix nanofilm; human vascular tissue; transplantation