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Circulation Research. 2009
Published online before print May 14, 2009, doi: 10.1161/CIRCRESAHA.108.190926
A more recent version of this article appeared on June 19, 2009
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Submitted on June 20, 2008
Revised on April 29, 2009
Accepted on May 4, 2009

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 ; Michael Murphy ; Brian H. Johnstone ; David A. Ingram ; and Keith L. March *

From the Department of Medicine (D.O.T., S.M.-C., A.R.S., B.H.J., K.L.M.); Indiana Center for Vascular Biology and Medicine (D.O.T., D.N.P., S.M.-C., A.R.S., M.M., B.H.J., D.A.I., K.L.M.); Department of Pediatrics (D.N.P., D.A.I.), Herman B. Wells Center for Pediatric Research; Department of Surgery (M.M.); Department of Biochemistry and Molecular Biology (D.A.I.); Department of Cellular and Integrative Physiology (K.L.M.), Indiana University School of Medicine; and R. L. Roudebush Veterans Affairs Medical Center (K.L.M.), Indianapolis, Ind.

* To whom correspondence should be addressed. E-mail: kmarch{at}iupui.edu.

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.


Key words: adipose stromal cells • endothelial cells • vasculogenesis • angiogenesis • tissue engineering • regenerative medicine • vascular networks


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J. Saif, C. Heeschen, and A. Aicher
Add Some Fat to Vascular Progenitor Cell Therapy
Circ. Res., June 19, 2009; 104(12): 1330 - 1332.
[Full Text] [PDF]