Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells

• Published in: Biomaterials Vol. 28; no. 17; pp. 2706 - 2717
• Main Authors: Ferreira, Lino S, Gerecht, Sharon, Fuller, Jason, Shieh, Hester F, Vunjak-Novakovic, Gordana, Langer, Robert
• Format: Journal Article
• Language: English
• Published: Netherlands 01-06-2007
• Subjects: Advanced Basic Science; Biomarkers - metabolism; Blood Vessels - cytology; Blood Vessels - drug effects; Cell Differentiation - drug effects; Cell Survival; Cells, Cultured; Dentistry; Dextrans - chemistry; Embryonic Stem Cells - cytology; Embryonic Stem Cells - drug effects; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Germ Layers - cytology; Glycolates - metabolism; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Hypoxia-Inducible Factor 1 - metabolism; Kinetics; Lactic Acid; Microspheres; Polyglycolic Acid; Protein Transport; Up-Regulation - genetics; Vascular Endothelial Growth Factor A - metabolism; Vascular Endothelial Growth Factor Receptor-2 - genetics; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Dextran; Hydrogel; Scaffold; Cell encapsulation; Stem cell; Endothelial cells
• ISSN: 0142-9612
• DOI: 10.1016/j.biomaterials.2007.01.021

Abstract We propose a new methodology to enhance the vascular differentiation of human embryonic stem cells (hESCs) by encapsulation in a bioactive hydrogel. hESCs were encapsulated in a dextran-based hydrogel with or without immobilized regulatory factors: a tethered RGD peptide and microencapsulated VEGF165 . The fraction of cells expressing vascular endothelial growth factor (VEGF) receptor KDR/Flk-1, a vascular marker, increased up to 20-fold, as compared to spontaneously differentiated embryoid bodies (EBs). The percentage of encapsulated cells in hydrogels with regulatory factors expressing ectodermal markers including nestin or endodermal markers including α -fetoprotein decreased 2- or 3-fold, respectively, as compared to EBs. When the cells were removed from these networks and cultured in media conditions conducive for further vascular differentiation, the number of vascular cells was higher than the number obtained through EBs, using the same media conditions. Functionalized dextran-based hydrogels could thus enable derivation of vascular cells in large quantities, particularly endothelial cells, for potential application in tissue engineering and regenerative medicine.