摘要
目的:评估采用血管内皮生长因子-A165(VEGF-A165)质粒联合粒细胞集落刺激因子(G-CSF)进行骨髓干细胞动员治疗严重慢性缺血性心脏病(IHD)患者的安全性和有效性。方法与结果:对16例严重慢性IH D患者予心肌内注射VEGF-A165质粒,1周后给予G-CSF[10μg/(kg·d),共6d]治疗。两对照组包括:①16例患者心肌内注射VEGF-A165质粒;②16例患者心肌内注射安慰剂。
Aims: To assess the safety and effects of combined treatment with vascular endothelial growth factor-A165(VEGF-A165)plasmid and granulocyte-colony stimulating factor(G-CSF) mobilization of bone marrow stem cells in patients with severe chronic ischaemic heart disease (IHD). Methods and results: Sixteen patients with severe chronic IHD were treated with intramyocardial injections of VEGF-A165 plasmid followed 1 week later by G-CSF (10 μg/kg/day for 6 days). Two control groups included (i) sixteen patients treated with intramyocardial injections of VEGF-A165 plasmid and (ii) sixteen patients treated with intramyocardial injections of placebo. In the G-CSF group, circulating CD34+stem cells increased almost 10-fold compared with the control groups (P< 0.0001). After 3 months, there was no improvement in myocardial perfusion at single photon emission computerized tomography in the VEGF-A165 and G-CSF treated group, and clinical symptoms were unchanged. There were no side effects to the gene and G-CSF therapy. Conclusion: Intramyocardial VEGF-A165 gene transfer followed by bone marrow stem cell mobilization with G-CSF seemed safe. However, a significant increase in circulating stem cells did not lead to improved myocardial perfusion or clinical effects suggesting a neutral effect of the treatment. To improve homing of stem cells, higher doses of VEGF-A165 and/or use of SDF-1 transfer might be considered.