VEGF profiling and angiogenesis in human microtissues.
Owing to its dual impact on tissue engineering (neovascularization of tissue implants) and cancer treatment (prevention of tumor-induced vascularization), management and elucidation of vascularization phenomena remain clinical priorities. Using a variety of primary human cells and (neoplastic) cell lines assembled in microtissues by gravity-enforced self-aggregation in hanging drops we (i) studied size and age-dependent VEGF production of microtissues in comparison to isogenic monolayer cultures, (ii) characterized the self-organization and VEGF-production potential of mixed-cell spheroids, (iii) analyzed VEGF-dependent capillary formation of human umbilical vein endothelial cells (HUVECs) cells coated onto several human primary cell spheroids, and (iv) profiled endostatin action on vascularization in human microtissues. Precise understanding of vascularization in human microtissues may foster advances in clinical tissue implant engineering, tumor treatment, as well as drug discovery and drug-function analysis.
Kelm
Jens M
JM
Institute for Chemical and Bio-Engineering, Swiss Federal Institute of Technology, ETH Hoenggerberg, HCI F115, Wolfgang-Pauli-Strasse 10, CH-8093 Zurich, Switzerland.
Diaz Sanchez-Bustamante
Carlota
C
Ehler
Elisabeth
E
Hoerstrup
Simon P
SP
Djonov
Valentin
V
Ittner
Lars
L
Fussenegger
Martin
M
D001011:Aorta / Q000166:cytology / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology / Q000648:ultrastructure; D005347:Fibroblasts / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods; D014471:Umbilical Veins / Q000166:cytology / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A