Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct

Jeroen Rouwkema, Jan de Boer, Clemens van Blitterswijk

Research output: Contribution to journalArticleAcademicpeer-review

242 Citations (Scopus)

Abstract

To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2% or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.
Original languageUndefined
Pages (from-to)2685-2693
JournalTissue engineering
Volume12
Issue number9
DOIs
Publication statusPublished - 2006

Keywords

  • METIS-236618
  • IR-67190

Cite this

@article{834f745295664d73bf732dc6fb2d50a1,
title = "Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct",
abstract = "To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2{\%} or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.",
keywords = "METIS-236618, IR-67190",
author = "Jeroen Rouwkema and {de Boer}, Jan and {van Blitterswijk}, Clemens",
year = "2006",
doi = "10.1089/ten.2006.12.2685",
language = "Undefined",
volume = "12",
pages = "2685--2693",
journal = "Tissue engineering",
issn = "1076-3279",
publisher = "Mary Ann Liebert Inc.",
number = "9",

}

Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct. / Rouwkema, Jeroen; de Boer, Jan; van Blitterswijk, Clemens.

In: Tissue engineering, Vol. 12, No. 9, 2006, p. 2685-2693.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Endothelial cells assemble into a 3-dimensional prevascular network in a bone tissue engineering construct

AU - Rouwkema, Jeroen

AU - de Boer, Jan

AU - van Blitterswijk, Clemens

PY - 2006

Y1 - 2006

N2 - To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2% or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.

AB - To engineer tissues with clinically relevant dimensions, one must overcome the challenge of rapidly creating functional blood vessels to supply cells with oxygen and nutrients and to remove waste products. We tested the hypothesis that endothelial cells, cocultured with osteoprogenitor cells, can organize into a prevascular network in vitro. When cultured in a spheroid coculture model with human mesenchymal stem cells, human umbilical vein endothelial cells (HUVECs) form a 3-dimensional prevascular network within 10 days of in vitro culture. The formation of the prevascular network was promoted by seeding 2% or fewer HUVECs. Moreover, the addition of endothelial cells resulted in a 4-fold upregulation of the osteogenic marker alkaline phosphatase. The addition of mouse embryonic fibroblasts did not result in stabilization of the prevascular network. Upon implantation, the prevascular network developed further and structures including lumen could be seen regularly. However, anastomosis with the host vasculature was limited. We conclude that endothelial cells are able to form a 3-dimensional (3D) prevascular network in vitro in a bone tissue engineering setting. This finding is a strong indication that in vitro prevascularization is a promising strategy to improve implant vascularization in bone tissue engineering.

KW - METIS-236618

KW - IR-67190

U2 - 10.1089/ten.2006.12.2685

DO - 10.1089/ten.2006.12.2685

M3 - Article

VL - 12

SP - 2685

EP - 2693

JO - Tissue engineering

JF - Tissue engineering

SN - 1076-3279

IS - 9

ER -