Premium
Engineering Blood Vessels from Lumenized Vascular Tissue Spheroids
Author(s) -
Drake Christopher,
Fleming Paul,
Forgacs Gabor,
Prestwich Glenn,
Mironov Vladimir
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a436-a
Subject(s) - spheroid , tissue engineering , vascular tissue , biomedical engineering , anatomy , medicine , chemistry , biology , botany , biochemistry , in vitro
We have applied the principle of VEGF‐mediated vascular fusion (Drake and Little, Proc Natl Acad Sci, 1995) to engineer blood vessels. Using the murine allantois as a source of endothelial precursor cells, spheroids were generated in hanging drop culture (HDC) that consist of an inner network of capillary‐sized vessels (CSV) and outer layers of alpha smooth muscle actin‐positive cells (SMAC). To transform spheroids into blood vessel‐like structures (BVLS), VEGF was used to induce the fusion of the CSV. This resulted in the formation of BVLS having a single endothelial‐lined lumen (dia. >300μm) surrounded by SMAC. Further, when two spheroids were exposed to VEGF in HDC, a single BVLS with an increased luminal diameter was formed. Essential to the use of spheroids in vascular engineering are 3D‐matrices that are permissive for both spheroid formation and vascular fusion. In studies evaluating a collagen hydrogel (CH) versus a cross‐linkable hyaluronan hydrogel (HH), we observed that HH but not CH was permissive for the formation of BVLS from spheroids. Finally, to demonstrate the utility of lumenized spheroids as modules to engineer blood vessels, we show that when multiple spheroids were exposed to VEGF in HH, they formed a single lumenized vascular tube‐like structure surrounded by SMAC. These findings validate our mathematical model of lumenized vascular spheroid fusion and demonstrate the feasibility of a tissue self‐assembly approach as a means of engineering blood vessels.