Robust functional vascular network formation in vivo by cooperation of adipose progenitor and endothelial cells

Dmitry O. Traktuev, Daniel N. Prater, Stephanie Merfeld-Clauss, Aravind Raj Sanjeevaiah, M. Reza Saadatzadeh, Michael Murphy, Brian H. Johnstone, David A. Ingram, Keith L. March

Research output: Contribution to journalArticle

247 Scopus citations

Abstract

Rapid induction and maintenance of blood flow through new vascular networks is essential for successfully treating ischemic tissues and maintaining function of engineered neo-organs. We have previously shown that human endothelial progenitor cells (EPCs) form functioning vessels in mice, but these are limited in number and persistence; and also that human adipose stromal cells (ASCs) are multipotent cells with pericytic properties which can stabilize vascular assembly in vitro. In this study, we tested whether ASCs would cooperate with EPCs to coassemble vessels in in vivo implants. Collagen implants containing EPCs, ASCs, or a 4:1 mixture of both were placed subcutaneously into NOD/SCID mice. After a range of time periods, constructs were explanted and evaluated with regard to vascular network assembly and cell fate; and heterotypic cell interactions were explored by targeted molecular perturbations. The density and complexity of vascular networks formed by the synergistic dual-cell system was many-fold higher than found in implants containing either ASCs or EPCs alone. Coimplantation of ASCs and EPCs with either pancreatic islets or adipocytes produced neoorgans populated by these parenchymal cells, as well as by chimeric human vessels conducting flow. This study is the first to demonstrate prompt and consistent assembly of a vascular network by human ASCs and endothelial cells and vascularization by these cells of parenchymal cells in implants. Mixture of these 2 readily available, nontransformed human cell types provides a practical approach to tissue engineering, therapeutic revascularization, and in vivo studies of human vasculogenesis.

Original languageEnglish (US)
Pages (from-to)1410-1420
Number of pages11
JournalCirculation research
Volume104
Issue number12
DOIs
StatePublished - Jun 19 2009

Keywords

  • Adipose stromal cells
  • Regenerative medicine
  • Tissue engineering
  • Vascular networks
  • Vasculogenesis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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