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Manipulating the microenvironment for vascular differentiation and regeneration
Author(s) -
Gerecht Sharon
Publication year - 2009
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.23.1_supplement.468.3
Subject(s) - vasculogenesis , microbiology and biotechnology , embryonic stem cell , extracellular matrix , angiogenesis , regeneration (biology) , nanotopography , stem cell , progenitor cell , regenerative medicine , chemistry , biology , anatomy , cancer research , biochemistry , gene
Microvasculature differentiation and regeneration is guided by both biochemical and biophysical cues. Human embryonic stem cells (hESCs) and adult endothelial progenitor cells (hEPCs), which are capabile to differentiate and form blood vessels de novo, can be used as a model system to elucidate vasculogenic and angiogenic mechanisms and explore central issues in vascular regeneration. Our goal is to understand the molecular mechanisms underlying human vascular differentiation and regeneration. To achieve this we exploit microengineering approaches to manipulate, study, and direct adult and embryonic stem cell differentiation. As an example, we found that the extracellular matrix polysaccharide hyaluronic acid (HA) is a developmentally relevant material for the growth of hESCs. Human ESCs encapsulated in HA hydrogels maintained undifferentiated and induced to initiate vasculogenesis by supplementation with VEGF. In continues studies, utilizing mechanically tunable HA hydrogels, we show that VEGF and matrix stiffness regulate angiogenesis from hEPCs. For the binding interactions between cells and surfaces, it has become increasingly evident that cells are influenced also by spatial domains, structural compositions, and mechanical forces at the microscale and nanoscale. We discovered that micro‐nanotopography of a substrate can be used to control vascular assembly and tubulogenesis.