Evidence of Accumulated Endothelial Progenitor Cells in the Lungs of Rats with Pulmonary Arterial Hypertension by 89Zr-oxine PET Imaging
Yimin Liu, Xin Zhao, Jie Ding, Yanjiang Xing, Meijun Zhou, Xuezhu Wang, Wenjia Zhu, Li Huo, Jun Yang
Abstract
Endothelial progenitor cells (EPCs) play a major role in regulating pulmonary vascular remodeling during pulmonary arterial hypertension (PAH) development. Several preclinical and clinical trials of EPCs transplantation have been performed for the treatment of PAH. However, there is no reliable method to monitor real-time cell trafficking and quantify transplanted EPCs. Here in this paper we isolated EPCs from human peripheral blood, identified their functional integrity, and efficiently labeled the EPCs with 89Zr-oxine and DiO. Labeled EPCs were injected into the tail vein of normal and PAH rats to be tracked in vivo. From the microPET/CT images, we found EPCs were distributed primarily in the lung at 1 h and then migrated to the liver and spleen. We could observe the 3,3′ dioctadecyloxacarbocyanine perchlorate (DiO)-labeled EPCs binding in the pulmonary vasculature by CellVizio confocal. The result of quantitative analysis revealed significantly higher accumulation of EPCs in the lungs of PAH rats than in those of healthy rats. The distribution and higher accumulation of EPCs in the lungs of PAH rats could help to evaluate the safety and provide evidence of effectiveness of EPC therapy. Endothelial progenitor cells (EPCs) play a major role in regulating pulmonary vascular remodeling during pulmonary arterial hypertension (PAH) development. Several preclinical and clinical trials of EPCs transplantation have been performed for the treatment of PAH. However, there is no reliable method to monitor real-time cell trafficking and quantify transplanted EPCs. Here in this paper we isolated EPCs from human peripheral blood, identified their functional integrity, and efficiently labeled the EPCs with 89Zr-oxine and DiO. Labeled EPCs were injected into the tail vein of normal and PAH rats to be tracked in vivo. From the microPET/CT images, we found EPCs were distributed primarily in the lung at 1 h and then migrated to the liver and spleen. We could observe the 3,3′ dioctadecyloxacarbocyanine perchlorate (DiO)-labeled EPCs binding in the pulmonary vasculature by CellVizio confocal. The result of quantitative analysis revealed significantly higher accumulation of EPCs in the lungs of PAH rats than in those of healthy rats. The distribution and higher accumulation of EPCs in the lungs of PAH rats could help to evaluate the safety and provide evidence of effectiveness of EPC therapy.