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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:802.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Amplification of Coronary Arteriogenic Capacity of Multipotent Stromal Cells by Epidermal Growth Factor

Souad Belmadani; Khalid Matrougui; Chris Kolz; Yuh Fen Pung; Desiree Palen; Darwin J. Prockop; William M. Chilian

From the Department of Physiology, LSUHSC, New Orleans, La; the Department of Physiology (K.M.), Tulane University Health Sciences Center, New Orleans, La; the Department of Integrative Medical Sciences (C.K., Y.F.P., W.M.C.), Northeastern Ohio Universities, College of Medicine; Texas A&M Health Science Center (D.J.P.), Institute for Regenerative Medicine, Temple, Tex.

Correspondence to William Chilian, PhD, Department of Integrative Medical Sciences, Northeastern Ohio Universities College of Medicine, 4209 State Road 44, Rootstown, OH 44272. E-mail wchilian{at}neoucom.edu

Objective— We determined whether increasing adherence of multipotent stromal cells (MSCs) would amplify their effects on coronary collateral growth (CCG).

Methods and Results— Adhesion was established in cultured coronary endothelials cells (CECs) or MSCs treated with epidermal growth factor (EGF). EGF increased MSCs adhesion to CECs, and increased intercellular adhesion molecule (ICAM-1) or vascular cell adhesion molecule (VCAM-1) expression. Increased adherence was blocked by EGF receptor antagonism or antibodies to the adhesion molecules. To determine whether adherent MSCs, treated with EGF, would augment CCG, repetitive episodes of myocardial ischemia (RI) were introduced and CCG was measured from the ratio of collateral-dependent (CZ) and normal zone (NZ) flows. CZ/NZ was increased by MSCs without treatment versus RI-control and was further increased by EGF-treated MSCs. EGF-treated MSCs significantly improved myocardial function versus RI or RI+MSCs demonstrating that the increase in collateral flow was functionally significant. Engraftment of MSCs into myocardium was also increased by EGF treatment.

Conclusions— These results reveal the importance of EGF in MSCs adhesion to endothelium and suggest that MSCs may be effective therapies for the stimulation of coronary collateral growth when interventions are used to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium.

Key Words: angiogenesis • collateral circulation • coronary circulation

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