Adipose Tissue Progenitor Cells Directly Interact with Endothelial Cells to Induce Vascular Network Formation
- 1 September 2010
- journal article
- research article
- Published by Mary Ann Liebert Inc in Tissue Engineering, Part A
- Vol. 16 (9), 2953-2966
- https://doi.org/10.1089/ten.tea.2009.0635
Abstract
Adipose stromal cells (ASCs) express markers and functional properties of pericytes in vitro and, in combination with endothelial cells (ECs), are able to establish multilayer functional vessels in vivo. However, the factors that coordinate EC-ASC communications to promote migration of these cells toward one another, and their heterotypic assembly into vascular structures are not well defined. To understand the mechanisms of EC-ASC interaction, we developed an in vitro model of coculturing ECs with ASCs in a system containing serum but no additional exogenous cytokines or extracellular matrix (ECM) proteins. We demonstrated that ASCs have a profound potential to stimulate morphogenesis of ECs into branching networks of cord structures. The vascular networks developed in 6 days and were stable for at least 3 weeks. This process was associated with an increase in ECM protein production by ASCs and ECs, α-smooth muscle actin expression by ASCs, and increased CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1) surface presentation by ECs. The vascular network formation (VNF) was dependent on matrix metalloproteinase activity and cell communications through vascular endothelial growth factor, hepatocyte growth factor, and platelet-derived growth factor-BB pathways. ASCs exhibited significantly higher potential to stimulate VNF than smooth muscle cells and fibroblasts. Media conditioned by ASCs promoted VNF by ECs cultured on smooth muscle cells and fibroblasts, but could not replace the presence of ASCs in coculture. The presence of ASCs in EC-fibroblast cocultures in a low fraction efficiently stimulated VNF. These findings demonstrate that the vasculogenesis-promoting potential of ASCs depends on interaction with ECs involving contact and likely bi-directional interaction, resulting in modulated secretion of cytokines and ECM proteins.Keywords
This publication has 43 references indexed in Scilit:
- MSC Frequency Correlates with Blood Vessel Density in Equine Adipose TissueTissue Engineering, Part A, 2009
- Differential gene expression in a coculture model of angiogenesis reveals modulation of select pathways and a role for Notch signalingPhysiological Genomics, 2009
- Human Aortic Smooth Muscle Cells Promote Arteriole Formation by Coengrafted Endothelial CellsTissue Engineering, Part A, 2009
- White Fat Progenitor Cells Reside in the Adipose VasculatureScience, 2008
- Engineering Robust and Functional Vascular Networks In Vivo With Human Adult and Cord Blood–Derived Progenitor CellsCirculation Research, 2008
- Differential in vivo potential of endothelial progenitor cells from human umbilical cord blood and adult peripheral blood to form functional long-lasting vesselsBlood, 2008
- Improvement of Postnatal Neovascularization by Human Adipose Tissue-Derived Stem CellsCirculation, 2004
- Secretion of Angiogenic and Antiapoptotic Factors by Human Adipose Stromal CellsCirculation, 2004
- Plasticity of Human Adipose Lineage Cells Toward Endothelial CellsCirculation, 2004
- Multilineage Cells from Human Adipose Tissue: Implications for Cell-Based TherapiesTissue Engineering, 2001