Boosting angiogenesis and functional vascularization in injectable dextran-hyaluronic acid hydrogels by endothelial-like mesenchymal stromal cells.
Angiogenesis and neovascularization are fundamental for the success of clinically relevant-sized tissue-engineered (TE) constructs. The next generation of TE constructs relies on providing instructive materials combined with the delivery of angiogenic growth factors and cells to avoid tissue ischemia. However, the majority of materials and cell types screened so far show limited clinical relevance, either due to insufficient number of cells or due to the use of animal-derived matrixes. Here, we investigated whether endothelial-like cells derived from mesenchymal stromal cells (EL-MSCs) can be used for vascular TE in combination with injectable dextran-hyaluronic acid (Dex-g-HA) hydrogels. These hydrogels can be easily modified, as demonstrated by the incorporation of vascular endothelial growth factor (VEGF). We examined in vitro the reciprocal influences between cells and matrix. Dex-g-HA enabled higher EL-MSC metabolic rates associated with optimal cell sprouting in vitro compared to human umbilical vein endothelial cells. In vivo evaluation demonstrated the absence of an acute inflammatory response, and EL-MSCs incorporated within Dex-g-HA formed a functional vascular network integrated with the host vascular system. This work demonstrates that Dex-g-HA is an efficient delivery method of VEGF to induce angiogenesis. Additionally, functional neovascularization can be achieved in vitro and in vivo by the combination of Dex-g-HA with EL-MSC.
1 Department of Tissue Regeneration, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
Karolina Janeczek
KJ
Portalska
Liliana Moreira
LM
Teixeira
Jeroen C H
JC
Leijten
Rong
R
Jin
Clemens
C
van Blitterswijk
Jan
J
de Boer
Marcel
M
Karperien
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002645:Chickens; D003911:Dextrans / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000494:pharmacology*; D020100:Hydrogels / Q000494:pharmacology*; D007249:Inflammation / Q000473:pathology; D007267:Injections; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D054457:Tissue Scaffolds / Q000737:chemistry
D015415:Biomarkers; D003911:Dextrans; D020100:Hydrogels; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D006820:Hyaluronic Acid