Induction of therapeutic neoangiogenesis using in vitro-generated endothelial colony-forming cells: an autologous transplantation model in rat

使用体外产生的内皮集落形成细胞诱导治疗性新血管生成:大鼠自体移植模型

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作者:Janina Jiga, Bogdan Hoinoiu, Teodora Stoichitoiu, Vlad Dornean, Alexandru Nistor, Sorin Barac, Gratian Miclaus, Mihai Ionac, Virgil Paunescu, Sorin Ursoniu, Lucian P Jiga

Background

Accumulating evidence shows the potential of bone marrow-derived endothelial colony-forming cells (bmECFCs) as promising tools for vascular repair. However, knowledge about their in vitro expansion, characterization, and functional behavior is still controversial. We demonstrate the in vitro generation of rat bmECFCs and analyze their ability to promote tissue reperfusion in a chronic hind-limb ischemia model.

Conclusions

We conclude that rat bmECFCs promote ischemic tissue reperfusion and their proangiogenic properties are a potential mechanism for this effect.

Methods

Either in vitro-generated and characterized autologous bmECFCs or placebo was injected into ischemic hind limbs of Sprague-Dawley rats. Tissue perfusion was quantified by laser Doppler, in perfusion units (PU), at days 0, 15, and 30.

Results

Rat bmECFCs acquire a typical phenotype (CD34(+)VEGFR2(+)CD133(+)CXCR4(+)CD45(-)), culture, and functional behavior (Dil-ac-LDL+) in vitro. Injection of autologous bmECFCs improves tissue perfusion in ischemic hind limbs (183.5 ± 3.29 PU(bmECFCs/day 30)versus 131 ± 3.9 PU(controls/day 30), P < 0.001). Conclusions: We conclude that rat bmECFCs promote ischemic tissue reperfusion and their proangiogenic properties are a potential mechanism for this effect.

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