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Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells.

Publication ,  Journal Article
Hanjaya-Putra, D; Yee, J; Ceci, D; Truitt, R; Yee, D; Gerecht, S
Published in: Journal of cellular and molecular medicine
October 2010

Endothelial progenitor cells (EPCs) in the circulatory system have been suggested to maintain vascular homeostasis and contribute to adult vascular regeneration and repair. These processes require that EPCs break down the extracellular matrix (ECM), migrate, differentiate and undergo tube morphogenesis. Evidently, the ECM plays a critical role by providing biochemical and biophysical cues that regulate cellular behaviour. Using a chemically and mechanically tunable hydrogel to study tube morphogenesis in vitro, we show that vascular endothelial growth factor (VEGF) and substrate mechanics co-regulate tubulogenesis of EPCs. High levels of VEGF are required to initiate tube morphogenesis and activate matrix metalloproteinases (MMPs), which enable EPC migration. Under these conditions, the elasticity of the substrate affects the progression of tube morphogenesis. With decreases in substrate stiffness, we observe decreased MMP expression while increased cellular elongation, with intracellular vacuole extension and coalescence to open lumen compartments. RNAi studies demonstrate that membrane type 1-MMP (MT1-MMP) is required to enable the movement of EPCs on the matrix and that EPCs sense matrix stiffness through signalling cascades leading to the activation of the RhoGTPase Cdc42. Collectively, these results suggest that coupled responses for VEGF stimulation and modulation of substrate stiffness are required to regulate tube morphogenesis of EPCs.

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Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

October 2010

Volume

14

Issue

10

Start / End Page

2436 / 2447

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Stem Cells
  • Microscopy, Electron, Transmission
  • Matrix Metalloproteinases
  • Male
  • Infant, Newborn
  • Hydrogels
  • Humans
  • Female
  • Extracellular Matrix
 

Citation

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Hanjaya-Putra, D., Yee, J., Ceci, D., Truitt, R., Yee, D., & Gerecht, S. (2010). Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells. Journal of Cellular and Molecular Medicine, 14(10), 2436–2447. https://doi.org/10.1111/j.1582-4934.2009.00981.x
Hanjaya-Putra, Donny, Jane Yee, Doug Ceci, Rachel Truitt, Derek Yee, and Sharon Gerecht. “Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells.Journal of Cellular and Molecular Medicine 14, no. 10 (October 2010): 2436–47. https://doi.org/10.1111/j.1582-4934.2009.00981.x.
Hanjaya-Putra D, Yee J, Ceci D, Truitt R, Yee D, Gerecht S. Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells. Journal of cellular and molecular medicine. 2010 Oct;14(10):2436–47.
Hanjaya-Putra, Donny, et al. “Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells.Journal of Cellular and Molecular Medicine, vol. 14, no. 10, Oct. 2010, pp. 2436–47. Epmc, doi:10.1111/j.1582-4934.2009.00981.x.
Hanjaya-Putra D, Yee J, Ceci D, Truitt R, Yee D, Gerecht S. Vascular endothelial growth factor and substrate mechanics regulate in vitro tubulogenesis of endothelial progenitor cells. Journal of cellular and molecular medicine. 2010 Oct;14(10):2436–2447.
Journal cover image

Published In

Journal of cellular and molecular medicine

DOI

EISSN

1582-4934

ISSN

1582-1838

Publication Date

October 2010

Volume

14

Issue

10

Start / End Page

2436 / 2447

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Stem Cells
  • Microscopy, Electron, Transmission
  • Matrix Metalloproteinases
  • Male
  • Infant, Newborn
  • Hydrogels
  • Humans
  • Female
  • Extracellular Matrix