The use of endothelial progenitor cells for prevascularized bone tissue engineering.
In vitro vascularization is an upcoming strategy to solve the problem of insufficient blood supply after implantation. Although recent publications show promising results, these studies were generally performed with clinically irrelevant endothelial cell model systems. We tested the use of endothelial progenitor cells (EPC) obtained from umbilical cord blood and human mesenchymal stem cells (hMSC) from the bone marrow for their use in a prevascularized bone tissue engineering setting. MSC were differentiated toward endothelial cells. They formed capillary-like structures containing lumen, stained positive for CD31, attained the ability to take up acetylated low-density lipoproteins, and formed perfused vessels in vivo. However, in a three-dimensional coculture setting with undifferentiated hMSC, the cells stopped expressing CD31 and did not form prevascular structures. EPC from the cord blood were able to form prevascular structures in the same coculture setting, but only when the state of endothelial differentiation was mature. The amount of prevascular structures formed when using EPC was less than when human umbilical vein endothelial cells or human dermal microvascular endothelial cells were used. The degree of organization, however, was higher. We conclude that EPC can be used for complex tissue engineering applications, but the differentiation stage of these cells is important.
Rouwkema
Jeroen
J
Departments of Biomechanical Engineering, Twente University, Enschede, The Netherlands. j.rouwkema@ctw.utwente.nl
Westerweel
Peter E
PE
de Boer
Jan
J
Verhaar
Marianne C
MC
van Blitterswijk
Clemens A
CA
D000328:Adult; D001842:Bone and Bones / Q000098:blood supply* / Q000502:physiology*; D002454:Cell Differentiation; D048430:Cell Shape; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D010012:Osteogenesis; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D018874:Spheroids, Cellular / Q000166:cytology; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering
D019408:Platelet Endothelial Cell Adhesion Molecule-1