Department of Vascular Surgery, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, People's Republic of China.
J Biomed Mater Res A. 2010 Nov;95(2):600-10. doi: 10.1002/jbm.a.32864.
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.
自体细胞再植是组织工程血管移植物领域的一个很有前途的挑战，内皮祖细胞（EPC）可以促进这一过程。本研究的目的是研究粒细胞集落刺激因子（G-CSF）治疗对此过程的影响。制备肝素固定化去细胞移植物并植入 48 只大鼠，其中 25 只大鼠在手术后 14 天接受 G-CSF（50ug/kg/天）治疗（G-CSF 组），其余 23 只接受生理盐水作为对照。每组各有 5 只动物在第 2 周处死，以分析早期移植物内皮化；其余动物通过多普勒超声监测移植物通畅率至 6 个月。G-CSF 给药 14 天后，CD(34)(+) / CD(133)(+)祖细胞数量增加了 16.2 倍，内皮细胞特异性免疫染色显示 G-CSF 组早期内皮化增强。植入 6 个月后，与对照组相比，G-CSF 治疗组的增生性新生内膜面积明显减小，不仅在中段（0.38 ± 0.02 对 0.47 ± 0.07mm(2)，p < 0.0001），而且在远端吻合处（0.42 ± 0.04 对 0.70 ± 0.13mm(2)，p < 0.0001）。此外，与对照组相比，G-CSF 治疗组的通畅率更高（19/20 对 12/18，p = 0.005）。总之，G-CSF 诱导的循环 EPC 动员再生了内皮，并抑制了肝素化小直径去细胞血管移植物的内膜增生。这种细胞因子治疗可能是提高新型同种异体移植物通畅率的可行策略。
