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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:758.)
© 2006 American Heart Association, Inc.

Vascular Biology

Differential Healing Activities of CD34⁺ and CD14⁺ Endothelial Cell Progenitors

Ola Awad; Eduard I. Dedkov; Chunhua Jiao; Steven Bloomer; Robert J. Tomanek; Gina C. Schatteman

From the Departments of Anatomy and Cell Biology (O.A., E.D., R.J.T.) and Exercise Science (C.J., S.B., G.C.S.), University of Iowa, Iowa City, Iowa.

Correspondence to Gina Schatteman, PhD, Exercise Science FH412, University of Iowa, Iowa City, IA 52242. E-mail gina-schatteman{at}uiowa.edu

Objective— Peripheral blood contains primitive (stem cell-like) and monocytic-like endothelial cell progenitors. Diabetes apparently converts these primitive progenitors, from a pro-angiogenic to anti-angiogenic phenotype. Monocytic progenitors seem to be less affected by diabetes, but potential pro-angiogenic activities of freshly isolated monocytic progenitors remain unexplored. We compared the ability of primitive and monocytic endothelial cell progenitors to stimulate vascular growth and healing in diabetes and investigated potential molecular mechanisms through which the cells mediate their in vivo effects.

Methods and Results— Human CD34⁺ primitive progenitors and CD14⁺ monocytic progenitors were injected locally into the ischemic limbs of diabetic mice. CD14⁺ cell therapy improved healing and vessel growth, although not as rapidly or effectively as CD34⁺ cell treatment. Western blot analysis revealed that cell therapy modulated expression of molecules in the VEGF, MCP-1, and angiopoietin pathways.

Conclusions— Injection of freshly isolated circulating CD14⁺ cells improves healing and vascular growth indicating their potential for use in acute clinical settings. Importantly, CD14⁺ cells could provide a therapeutic option for people with diabetes, the function of whose CD34⁺ cells may be compromised. At least some progenitor-induced healing probably is mediated through increased sensitivity to VEGF and increases in MCP-1, and possibly modulation of angiopoietins.

Human CD34⁺ and CD14⁺ blood-derived endothelial cell progenitors were injected into ischemic limbs of diabetic mice. CD14⁺ cell therapy accelerated healing, although not as much as CD34⁺ cell treatment. Nevertheless, CD14⁺ cells could provide a therapeutic option for diabetic patients, the function of whose CD34⁺ cells may be compromised.

Key Words: angiogenesis • CD34 • diabetes • endothelial progenitor cells • monocytes

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