内皮原生细胞血管内皮生长因子基因转移用于血管再生
Hideki Iwaguro1, Jun-ichi Yamaguchi, Christoph Kalka
1Division of Cardiovascular Research and Medicine, St Elizabeth's Medical Center, Tufts University School of Medicine, Boston, Mass 02135, USA.
Circulation
|February 13, 2002
概括
基因转移增强了内皮原生细胞 (EPC),以促进血管生长. 修改后的EPC在动物模型中改善了血液流动并减少了四肢损伤,需要较低的细胞剂量才能产生治疗效果.
科学领域:
- 再生医学是一种再生医学.
- 血管生物学 血管生物学
- 基因治疗 基因治疗
背景情况:
- 内皮原生细胞 (EPC) 在血液中循环.
- 研究调节EPC功能的基因转移.
研究的目的:
- 评估基因转移是否可以增强EPC用于治疗性新血管化.
- 在四肢缺血模型中评估VEGF修饰EPC的疗效.
主要方法:
- 在实验室中将VEGF 164的基因转移到小鼠EPC中.
- 评估EPC的扩散,粘附和融入内皮单层.
- 在体内给予VEGF转化EPCs给后肢缺血的小鼠.
主要成果:
- VEGF基因转移增加了EPC的扩散,粘附和结合.
- 转化EPCs改善了缺血四肢的新血管化和血液流量恢复.
- 与之前的研究相比,肢体缩减少了63.7%,细胞剂量明显降低.
结论:
- 在体外,VEGF基因转移有效地增强了EPC功能.
- 基因改造的EPCs代表了增强缺血性疾病中新血管化的有前途战略.
相关概念视频
Mechanism of Angiogenesis
Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
Regulation of Angiogenesis and Blood Supply
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...


