Abstract 11666: Targeted Delivery of Rat iPS-Endothelial Cells Overexpressing Neutrophil IL8-RA/RB or Macrophage CCR2/CCR5 Receptors Inhibits Neointima Formation in Balloon Injured Rat Carotid Artery
Introduction: Interleukin 8 Receptors A and B (IL8RA and IL8RB) and C-C chemokine receptors 2 and 5 (CCR2 and CCR5) found on neutrophil and macrophage membranes respectively, modulate leukocyte chemotaxis after vascular injury. We have generated targeted cell therapy using adenoviral vectors that contain full length IL8RA, IL8RB, CCR2 and CCR5 cDNAs and green fluorescent protein. Transduced endothelial cells differentiated from rat induced pluripotent stem cells (RiPS-ECs) overexpressing these receptors provides support for autologous targeted cell therapy. We hypothesize that transfusion of RiPS-EC overexpressing IL8RA/B (RiPS-IL8RA/B-ECs), CCR2/5 (RiPS-CCR2/5-ECs) or both IL8RA/B and CCR2/5 (RiPS-IL8RA/B+CCR2/5-EC) into rats with balloon injury of the carotid artery will target to the area of injury, decrease the inflammatory response, and inhibit neointima formation. We will further determine the individual contribution of neutrophils and macrophage in the acute vascular injury response.
Methods: 12 wk old male Sprague-Dawley rats received balloon injury of the right carotid artery and were immediately administered i.v. transfusion of 1) saline vehicle, 2)1.5x106 RiPS-Null-ECs; 3)1.5x106 RiPS-IL8RA/B-ECs, 4) 1.5x106 RiPS-CCR2/5-ECs, 6)1.5x106 RiPS-IL8RA/B+CCR2/5-ECs. One group of rats was sacrificed 24 hr post injury and cell transfusion and infiltration of neutrophils and monocytes/macrophages and pro-inflammatory cytokine levels were measured. A second group of rats was sacrificed 2 wks post injury for measurement of neointima formation.
Results: RiPS-ECs equipped with the IL8RA/B or CCR2/5 homing device mimic the behavior of leukocytes and target to the injured arteries and inhibited neointima formation after endoluminal injury. Conclusions: These findings indicate a novel treatment for vascular injury using targeted cell therapy against both neutrophils and macrophages.
Author Disclosures: S. Giordano: None. D. Xing: None. F.G. Hage: None. T.M. Townes: None. C. Sun: None. L. Wu: None. S. Oparil: None. Y. Chen: None.
- © 2015 by American Heart Association, Inc.