Amplification of coronary arteriogenic capacity of multipotent stromal cells by epidermal growth factor.
Amplification of coronary arteriogenic capacity of multipotent stromal cells by epidermal growth factor.
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DOI：
10.1161/atvbaha.109.186189
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发表时间：
2009-06
期刊：
影响因子：
--
通讯作者：
Chilian WM
中科院分区：
文献类型：
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作者：
Belmadani S;Matrougui K;Kolz C;Pung YF;Palen D;Prockop DJ;Chilian WM
我们确定了增加多能基质细胞(MSCs)的黏附率是否会放大它们对冠状动脉侧枝生长(CCG)的影响。在培养的冠状动脉内皮细胞(CECs)或经表皮生长因子(EGF)处理的MSCs上建立黏附。EGF促进MSCs与CECs的黏附，增加细胞间黏附分子(ICAM-1)或血管细胞黏附分子(VCAM-1)的表达。EGF受体拮抗剂或针对黏附分子的抗体可阻断黏附增加。为了确定经EGF处理的贴壁MSCs是否会增加CCG，我们引入了重复的心肌缺血(RI)发作，并根据侧支依赖(CZ)和正常区(NZ)血流的比率来测量CCG。未经处理的MSCs与RI对照组相比，Cz/NZ增加，经EGF处理的MSCs进一步增加。与RI或RI+MSCs相比，经EGF处理的MSCs明显改善心肌功能，说明侧支循环血流量的增加在功能上是显着的。EGF还能增加MSCs在心肌中的植入。这些结果揭示了EGF在MSCs与内皮细胞黏附中的重要性，并提示当采用干预措施增加MSCs对受损心肌的黏附和归巢(体外EGF治疗)时，MSCs可能是刺激冠脉侧支生长的有效治疗方法。
We determined if increasing adherence of multipotent stromal cells (MSCs) would amplify their effects on coronary collateral growth (CCG). Adhesion was established in cultured coronary endothelials cells (CECS) or MSCs treated with epidermal growth factor (EGF). EGF increased MSCs adhesion to CECs, and increased intercellular adhesion molecule (ICAM-1) or vascular cell adhesion molecule (VCAM-1) expression. Increased adherence was blocked by EGF receptor antagonism or antibodies to the adhesion molecules. To determine if adherent MSCs, treated with EGF, would augment CCG, repetitive episodes of myocardial ischemia (RI) were introduced and CCG was measured from the ratio of collateral-dependent (CZ) and normal zone (NZ) flows. CZ/NZ was increased by MSCs without treatment vs RI-control and was further increased by EGF-treated MSCs. EGF-treated MSCs significantly improved myocardial function vs RI or RI+ MSCs demonstrating that the increase in collateral flow was functionally significant. Engraftment of MSCs into myocardium was also increased by EGF treatment. These results reveal the importance of EGF in MSCs adhesion to endothelium and suggest that MSCs may be effective therapies for the stimulation of coronary collateral growth when interventions are employed to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium.