Faculty Collaboration Database

Spontaneous fibroblast-derived pericyte recruitment in a human tissue-engineered angiogenesis model in vitro. J Cell Physiol 2012 May;227(5):2130-7

Date

07/20/2011

Pubmed ID

21769871

DOI

10.1002/jcp.22943

Scopus ID

2-s2.0-84856170502 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

Cooperation between endothelial cells and pericytes is essential to the stabilization and maturation of blood microvessels. We developed a unique in vitro tissue-engineered model to study angiogenesis. The human endothelialized reconstructed connective tissue model promotes the formation of a three-dimensional branching network of capillary-like tubes (CLT) with closed lumens. The purpose of this work was to investigate whether pericytes were spontaneously recruited around CLT in the model. We demonstrated that smooth muscle α-actin (SMA)-positive cells were found closely associated with PECAM-1-positive capillaries in the model. Twelve percent (±2.6) of SMA-positive cells were detected along with 15% (±1.64) von Willebrand factor-positive endothelial cells in the culture system after 31 days of in vitro maturation. Conversely, no SMA-positive cells were detected in reconstructed connective tissues made solely of fibroblasts. Knowing that PDGF is a major factor in the recruitment of pericytes, we showed that blockade of the PDGFB receptor using the inhibitor AG1296 induced an overall 5, 2.6, and 2.4-fold decrease in the SMA-positive cells, von Willebrand factor-positive cells, and number of capillaries, respectively. Using combinations of human GFP-positive fibroblasts and endothelial cells, we demonstrated that pericytes were recruited from the fibroblast population in the model. In conclusion, our tissue-engineered culture system promotes the spontaneous formation of a network of capillaries and the recruitment of pericytes derived from fibroblasts. Since pericytes are essential components of the blood microvasculature, this culture system is a powerful model to study angiogenesis and endothelial cell/pericyte interactions in vitro.

Author List

Berthod F, Symes J, Tremblay N, Medin JA, Auger FA

Author

Jeffrey A. Medin PhD Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Actins
Capillaries
Cell Culture Techniques
Fibroblasts
Human Umbilical Vein Endothelial Cells
Humans
Infant, Newborn
Models, Cardiovascular
Neovascularization, Physiologic
Pericytes
Platelet Endothelial Cell Adhesion Molecule-1
Proto-Oncogene Proteins c-sis
Receptor, Platelet-Derived Growth Factor beta
Tissue Engineering
von Willebrand Factor