Transplantation of Monocytes: A Novel Strategy for In Vivo Augmentation of Collateral Vessel Growth

Abstract

Therapeutic augmentation of collateral vessel growth (arteriogenesis) is of particular clinical interest. Because monocytes localize to areas of collateral growth and create a highly arteriogenic environment through secretion of multiple growth factors, we tested the hypothesis that monocyte "homing" can therapeutically be exploited. We have used a rabbit model of arteriogenesis to investigate the therapeutic potential of transplanted rabbit monocytes that were either ex vivo stimulated or adenovirally transduced to express a transgene encoding an arteriogenic growth factor. The monocytes were intravenously injected 24 hr or 7 days after ligation of the animal's right femoral artery. Seven days after transplantation collateral flow was determined with a doppler flow probe and collateral vessels were quantified angiographically. Whereas transplantation of allogeneic cells (same species) resulted in a strong promotion of arteriogenesis, most likely through induction of local inflammation and recruitment of recipient monocytes, transplantation of autologous cells (same animal) was not able to significantly augment collateralization. However, when autologous monocytes were used as vehicles to deliver granulocyte macrophage-colony stimulating factor as therapeutic transgene, collateralization was strongly augmented. Their localization to the site of collateral development posttransplantation was demonstrated by ex vivo transduction with β-galactosidase. Because isolation of monocytes is clinically widely available their ex vivo engineering and transplantation represents an intriguing new strategy for therapeutic arteriogenesis.