Repeated CXCR4 Blockade by Plerixafor Attenuates Transplant Vasculopathy in Murine Aortic Allografts

Plerixafor, a hematopoietic stem cell mobilization agent, increases the peripheral blood content of effector and regulatory T cells and may have beneficial effects on cardiac allograft vasculopathy. The aim of the current study was to evaluate its effects in a murine aortic allograft model using different application procedures. Allogeneic donor aorta grafts (n = 8/group) from C57BL/6 mice(H2b) were abdominally transplanted into CBA mice (H2k). Plerixafor application was performed either continuously for 14 d using abdominally implanted osmotic pumps (1 mg/kg/d) or i.p. with a single dose (1 and 5 mg/kg) on day 0 or pulsed injections of 1 mg/kg on days 0, 7, 14, and 21. Cell distribution was monitored by FACS. Aortic grafts were evaluated for neointima development by Elastica-van-Gieson on day 30. Immunofluorescence and intragraft gene expression analysis were performed. On day 14, significantly fewer hematopoietic stem cells were found in the bone marrow of all plerixafor-treated mice. In the pulsed application group, significantly more hematopoietic stem cells were found in the peripheral blood on day 14 (0.045 ± 0.002%; p