Hou Dongming, Youssef Eyas Al-Shaykh, Brinton Todd J, Zhang Ping, Rogers Pamela, Price Erik T, Yeung Alan C, Johnstone Brian H, Yock Paul G, March Keith L
Indiana University School of Medicine, Indianapolis, IN, USA.
Circulation. 2005 Aug 30;112(9 Suppl):I150-6. doi: 10.1161/CIRCULATIONAHA.104.526749.
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.
Myocardial ischemia was created by 45 minutes of balloon occlusion of the left anterior descending coronary artery. Six days later, 10(7) 111indium-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.
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.
多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，对于任何细胞类型，所移植细胞的实际命运尚未得到全面评估。我们在缺血性猪模型中评估了经心肌内（IM）、冠状动脉内（IC）和逆行冠状静脉间质（IRV）移植后外周血单个核细胞（PBMNC）的短期命运。
通过球囊阻塞左前降支冠状动脉45分钟造成心肌缺血。6天后，通过IC（n = 5）、IM（n = 6）或IRV（n = 5）注射移植10⁷铟 - 奥辛标记的人PBMNC。通过对收获器官进行γ发射计数来评估注射细胞的分布。对于每种移植方法，相当一部分移植细胞离开心脏进入肺循环，分别有26±3%（IM）、47±1%（IC）和43±3%的细胞定位于肺。在心肌内，与IC移植（2.6±0.3%）相比，IM注射后保留的细胞明显更多（11±3%）（P<0.05）。对于PBMNC，IRV移植效率（3.2±1%）略低于IM输注，但差异无统计学意义。与其他技术相比，IM技术在移植效率方面表现出最大的变异性。
对于每种移植方式，大多数移植细胞并未保留在心脏中。这些发现的临床意义可能很大，因为具有促血管生成或其他治疗作用的细胞可能会在其并非主要靶向但却会分布到的其他器官中产生影响。此外，我们发现尽管IM注射更有效，但与IC和IRV技术相比，在PBMNC移植方面其一致性较差。
