Beneficial effects of granulocyte-colony stimulating factor on small-diameter heparin immobilized decellularized...

Autologous recellularization of decellularized scaffolds is a promising challenge in the field of tissue-engineered vascular graft and could be boosted by endothelial progenitor cells (EPCs). The purpose of this study was to examine the effects of granulocyte-colony stimulating factor (G-CSF) treatment on this process. Heparin immobilized decellularized grafts were fabricated and implanted into 48 rats, of which 25 rats received G-CSF (50 ug/kg/day) for 14 days after operation (G-CSF group) and other 23 received saline serving as control. Five animals of each group were euthanized at 2 weeks for analysis of early graft endothelialization; whereas the rest were investigated by Doppler ultrasound to monitor the graft patency rate up to 6 months. After 14 days of G-CSF administration, the number of CD(34) (+)/CD(133) (+) progenitor cells was increased by 16.2 folds, and endothelial cell-specific immunostaining revealed an enhancement of early endothelialization in G-CSF group. After 6 months of implantation, the G-CSF treated grafts exhibited a significantly smaller hyperplastic neointima area compared with the controls, not only at midportion (0.38 ± 0.02 vs. 0.47 ± 0.07 mm(2), p < 0.0001), but also at distal anastomosis (0.42 ± 0.04 vs. 0.70 ± 0.13 mm(2), p < 0.0001). Moreover, G-CSF treated grafts had a higher patency rate compared with the control animals (19/20 vs. 12/18, p = 0.005). In conclusion, G-CSF-induced mobilization of circulating EPCs regenerated endothelium and inhibited neointimal hyperplasia of small-diameter heparinized decellularized vascular graft. This cytokine therapy may be a feasible strategy for the improvement of patency rate of the novel allogeneic graft.