Saltzman Adam J, Choi Sung W, Dabreo Alexandra, Baur Wendy E, Weiss Eric, Nguyen Khan, Ishibashi Fumiyuki, Celestin Flore F, Karia Darshak H, Pandian Natesa G, Karas Richard H, Waxman Sergio
Division of Cardiology, Tufts Medical Center, Boston, MA, USA.
Cardiovasc Revasc Med. 2010 Oct-Dec;11(4):241-8. doi: 10.1016/j.carrev.2009.06.003.
Our objective was to determine whether autologous endothelial progenitor cells (EPCs) delivered into the pericardial space will migrate to and incorporate into ischemic myocardium in a porcine model.
Use of EPCs to enhance neovascularization and preserve myocardial function in ischemic tissue is undergoing intense scrutiny as a potential therapy. Delivery into the pericardial sac may overcome some of the limitations of currently employed cell delivery techniques.
EPCs were immunopurified from peripheral blood of Yorkshire pigs by selecting for the CD31 surface antigen, and adherent cells were cultured for 3-5 days. After myocardial ischemia was induced in the left anterior descending (LAD) artery, either autologous DiI (1,1'-dioctadecyl-1-3,3,3',3'-tetramethylindocarbocyanine perchlorate)-labeled EPCs (n=10) or serum-free medium (SFM; n=8) was delivered into the pericardial space using a percutaneous transatrial approach. Animals were sacrificed on Day 7 or 21. Echocardiography was performed at baseline, during ischemia, and on Day 7 in six SFM group animals and six EPC group animals.
On Day 7, EPCs were identified in the left ventricular (LV) anterior wall or anterior septum in all six EPC-treated animals (cell density of 626 ± 122/mm(2)). On Day 21, EPCs were identified in the LV anterior wall or anterior septum in three of four EPC-treated animals (cell density of 267 ± 167/mm(2)). These cells showed dual staining for DiI and Bandeiraea simplicifolia lectin I (a marker of both native and exogenous endothelial cells). At the Day 7 follow-up, echocardiography demonstrated that fractional shortening in the EPC-treated group was 30.6 ± 3.4, compared with 22.6 ± 2.8 in SFM controls (P=.05).
EPCs can migrate from the pericardial space to incorporate exclusively into areas of ischemic myocardium and may have favorable effects on LV function.
我们的目的是确定在猪模型中，注入心包腔的自体内皮祖细胞（EPCs）是否会迁移至缺血心肌并整合其中。
作为一种潜在治疗方法，使用EPCs增强缺血组织中的新生血管形成并维持心肌功能正受到密切关注。注入心包囊可能克服当前所用细胞递送技术的一些局限性。
通过选择CD31表面抗原，从约克夏猪外周血中免疫纯化EPCs，并将贴壁细胞培养3 - 5天。在左前降支（LAD）动脉诱导心肌缺血后，使用经皮经心房方法将自体DiI（1,1'-二辛基-1-3,3,3',3'-四甲基吲哚羰花青高氯酸盐）标记的EPCs（n = 10）或无血清培养基（SFM；n = 8）注入心包腔。在第7天或第21天处死动物。在基线、缺血期间以及第7天，对6只SFM组动物和6只EPC组动物进行超声心动图检查。
在第7天，所有6只接受EPC治疗的动物的左心室（LV）前壁或前间隔中均发现了EPCs（细胞密度为626 ± 122/mm²）。在第21天，4只接受EPC治疗的动物中有3只在LV前壁或前间隔中发现了EPCs（细胞密度为267 ± 167/mm²）。这些细胞对DiI和简单叶豆凝集素I（天然和外源性内皮细胞的标志物）呈双重染色。在第7天的随访中，超声心动图显示，EPC治疗组的心内膜缩短分数为30.6 ± 3.4，而SFM对照组为22.6 ± 2.8（P = 0.05）。
EPCs可从心包腔迁移并专门整合到缺血心肌区域，可能对左心室功能产生有利影响。
