Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery - Implications for current clinical trials
Radiolabeled cell distribution after intramyocardial, intracoronary, and interstitial retrograde coronary venous delivery - Implications for current clinical trials
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DOI：
10.1161/circulationaha.104.526749
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发表时间：
2005-08-30
期刊：
影响因子：
37.8
通讯作者：
March, KL
中科院分区：
文献类型：
--
作者：
Hou, DM;Youssef, EAS;March, KL
背景-几项临床研究正在评估各种祖细胞移植治疗受损心脏的治疗潜力。然而，对于任何类型的细胞，交付细胞的实际命运还没有得到彻底的评估。我们评估了心肌内(IM)、冠状动脉内(IC)和间质逆行冠状动脉静脉(IRV)注射后外周血单个核细胞(PBMNCs)的短期命运。方法和结果-球囊闭塞左冠状动脉前降支45min造成心肌缺血。6天后，10(7)(111)个铟-oxine标记的人PBMNCs分别经IC(n=5)、IM(n=6)或IRV(n=5)注射。通过采集器官的伽马发射计数来评估注射细胞的分布。对于每种递送方式，相当一部分被输送的细胞离开心脏进入肺循环，其中26+/-3%(IM)、47+/-1%(IC)和43+/-3%(IRV)的细胞定位于肺部。在心肌内，IM注射后的细胞存留率(11+/-3%)显著高于IC注射后(2.6+/-0.3%)(P<；0.05)。IRV输注效率(3.2+/-1%)较IM输注有下降趋势，但差异无统计学意义。与其他技术相比，IM技术显示出最大的传递效率差异。结论-对于每种传递方式，大部分传递细胞并未保留在心脏中。这些发现的临床意义具有潜在的重大意义，因为可以想象，具有促血管生成或其他治疗作用的细胞可能会对它们主要不是针对的其他器官产生影响，但它们是分布到这些器官的。此外，我们还发现，尽管IM注射效率更高，但与IC和IRV技术相比，它在PBMNCs的传递方面的一致性较差。
Background-Several clinical studies are evaluating the therapeutic potential of delivery of various progenitor cells for treatment of injured hearts. However, the actual fate of delivered cells has not been thoroughly assessed for any cell type. We evaluated the short-term fate of peripheral blood mononuclear cells (PBMNCs) after intramyocardial (IM), intracoronary (IC), and interstitial retrograde coronary venous (IRV) delivery in an ischemic swine model.Methods and Results-Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) (111)indium-oxine-labeled human PBMNCs were delivered by IC (n=5), IM (n=6), or IRV (n=5) injection. The distribution of injected cells was assessed by gamma-emission counting of harvested organs. For each delivery method, a significant fraction of delivered cells exited the heart into the pulmonary circulation, with 26 +/- 3% (IM), 47 +/- 1% (IC), and 43 +/- 3% (IRV) of cells found localized in the lungs. Within the myocardium, significantly more cells were retained after IM injection (11 +/- 3%) compared with IC (2.6 +/- 0.3%) (P < 0.05) delivery. IRV delivery efficiency (3.2 +/- 1%) trended lower than IM infusion for PBMNCs, but this difference did not reach significance. The IM technique displayed the greatest variability in delivery efficiency by comparison with the other techniques.Conclusions-The majority of delivered cells is not retained in the heart for each delivery modality. The clinical implications of these findings are potentially significant, because cells with proangiogenic or other therapeutic effects could conceivably have effects in other organs to which they are not primarily targeted but to which they are distributed. Also, we found that although IM injection was more efficient, it was less consistent in the delivery of PBMNCs compared with IC and IRV techniques.