Smooth Muscle Progenitor Cells in Human Blood
- 3 September 2002
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation
- Vol. 106 (10), 1199-1204
- https://doi.org/10.1161/01.cir.0000031525.61826.a8
Abstract
Background— Recent animal data suggest that vascular smooth muscle cells within the neointima of the vessel wall may originate from bone marrow, providing indirect evidence for circulating smooth muscle progenitor cells (SPCs). Evidence for circulating SPCs in human subjects does not exist, and the mechanism whereby such putative SPCs may home to sites of plaque formation is presently not understood but is likely to involve expression of specific surface adhesion molecules, such as integrins. In this study, we aimed to culture smooth muscle outgrowth cells (SOCs) from SPCs in human peripheral blood and characterize surface integrin expression on these cells. Methods and Results— Human mononuclear cells isolated from buffy coat were seeded on collagen type 1 matrix and outgrowth cells selected in endothelial growth medium (EGM-2) or EGM-2 and platelet-derived growth factor BB. Selection in platelet-derived growth factor BB–enriched medium caused rapid outgrowth and expansion of SOC to >40 population doublings in a 4-month period. These SOCs were positive for smooth muscle cell–specific α actin (αSMA), myosin heavy chain, and calponin on immunofluorescence and Western blotting and were also positive for CD34, Flt1, and Flk1 receptor but negative for Tie-2 receptor expression, suggesting a potential bone marrow angioblastic origin. In contrast, endothelial outgrowth cells (EOCs) grown in EGM-2 alone and the initial MNC population were negative for these smooth muscle–specific markers. Integrin α 5 β 1 expression by FACS and Western blotting was significantly increased in SOCs compared with EOCs, and this was confirmed by 8-fold greater adhesion of SOC to fibronectin ( P 5 β 1 antibody. Finally, SOC showed a significantly greater in vitro proliferative potential compared with EOCs of similar passage ( P Conclusions— This study demonstrates for the first time outgrowth of smooth muscle cells with a specific growth, adhesion, and integrin profile from putative SPC in human blood. These data have implications for our understanding of adult vascular smooth muscle cell differentiation, proliferation, and homing. (Circulation. 2002;106:1199–1204.)Keywords
This publication has 23 references indexed in Scilit:
- Ex vivo expansion of umbilical cord blood (UCB) CD34+ cells alters the expression and function of α4β1 and α5β1 integrinsBritish Journal of Haematology, 2001
- Association between plaque instability, angiogenesis and symptomatic carotid occlusive diseaseBritish Journal of Surgery, 2001
- Origin of neointimal endothelium and α-actin–positive smooth muscle cells in transplant arteriosclerosisJCI Insight, 2001
- Origins of circulating endothelial cells and endothelial outgrowth from bloodJCI Insight, 2000
- PDGF, TGF-β, and Heterotypic Cell–Cell Interactions Mediate Endothelial Cell–induced Recruitment of 10T1/2 Cells and Their Differentiation to a Smooth Muscle FateThe Journal of cell biology, 1998
- Cell Adhesion Receptors for Native and Denatured Type I Collagens and Fibronectin in Rabbit Arterial Smooth Muscle Cells in CultureExperimental Cell Research, 1994
- Inhibition of human vascular smooth muscle cell growth by heparinThe Lancet, 1994
- The pathogenesis of atherosclerosis: a perspective for the 1990sNature, 1993
- A gentle fixation and permeabilization method for combined cell surface and intracellular staining with improved precision in DNA quantificationCytometry, 1991
- PDGF ligand and receptor gene expression during repair of arterial injury.The Journal of cell biology, 1990