Bioactive hydrogel scaffolds for controllable vascular differentiation of human embryonic stem cells.
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 VEGF(165). 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 alpha-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.
Ferreira
Lino S
LS
Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Gerecht
Sharon
S
Fuller
Jason
J
Shieh
Hester F
HF
Vunjak-Novakovic
Gordana
G
Langer
Robert
R
D015415:Biomarkers / Q000378:metabolism; D001808:Blood Vessels / Q000166:cytology* / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D003911:Dextrans / Q000737:chemistry; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005855:Germ Layers / Q000166:cytology; D006016:Glycolates / Q000378:metabolism; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000494:pharmacology*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007700:Kinetics; D019344:Lactic Acid; D008863:Microspheres; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D021381:Protein Transport; D015854:Up-Regulation / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D003911:Dextrans; D006016:Glycolates; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011100:Polyglycolic Acid; D019344:Lactic Acid; D040301:Vascular Endothelial Growth Factor Receptor-2