Adipose tissue progenitor cells directly interact with endothelial cells to induce vascular network formation

Stephanie Merfeld-Clauss, Nagesh Gollahalli, Keith L. March, Dmitry Traktuev

Research output: Contribution to journalArticle

111 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2953-2966
Number of pages14
JournalTissue Engineering - Part A
Volume16
Issue number9
DOIs
StatePublished - Sep 1 2010

Fingerprint

Endothelial cells
Stromal Cells
Blood Vessels
Adipose Tissue
Stem Cells
Endothelial Cells
Tissue
Extracellular Matrix Proteins
Fibroblasts
Muscle
Cell Communication
Cells
Platelets
Proteins
Coculture Techniques
Smooth Muscle Myocytes
CD31 Antigens
Cytokines
Hepatocyte Growth Factor
Communication

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomedical Engineering
  • Biomaterials
  • Medicine(all)

Cite this

Adipose tissue progenitor cells directly interact with endothelial cells to induce vascular network formation. / Merfeld-Clauss, Stephanie; Gollahalli, Nagesh; March, Keith L.; Traktuev, Dmitry.

In: Tissue Engineering - Part A, Vol. 16, No. 9, 01.09.2010, p. 2953-2966.

Research output: Contribution to journalArticle

Merfeld-Clauss, Stephanie ; Gollahalli, Nagesh ; March, Keith L. ; Traktuev, Dmitry. / Adipose tissue progenitor cells directly interact with endothelial cells to induce vascular network formation. In: Tissue Engineering - Part A. 2010 ; Vol. 16, No. 9. pp. 2953-2966.
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