Fuchs Shmuel, Kornowski Ran, Weisz Giora, Satler Lowell F, Smits Peter C, Okubagzi Petros, Baffour Richard, Aggarwal Anita, Weissman Neil J, Cerqueira Manuel, Waksman Ron, Serrruys Parrick, Battler Alexander, Moses Jeffrey W, Leon Martin B, Epstein Stephen E
Rabin Medical Center, Petach-Tikva, Israel.
Am J Cardiol. 2006 Mar 15;97(6):823-9. doi: 10.1016/j.amjcard.2005.09.132. Epub 2006 Jan 30.
The present report contains the final results of a Phase I study that evaluated the feasibility, safety, and potential efficacy of intramyocardial injection of autologous bone marrow (BM) in "no-option" patients with refractory angina and myocardial ischemia. Twenty-seven patients underwent electromechanic mapping-guided transendomyocardial injections (n = 12, 0.2 ml each) of unfractionated autologous BM cells directed to ischemic, noninfarcted myocardial territory. Patients were injected with 28 +/- 27 x 10(6)/ml nucleated cells containing 2.2 +/- 1.4% CD34+ cells. The autologous BM injection procedure was successful in all patients and was associated with no adverse events. At 3 months, the Canadian Cardiovascular Society angina score (3.2 +/- 0.5 vs 2.0 +/- 0.91, p = 0.001) and treadmill exercise duration (418 +/- 136 vs 489 +/- 142 seconds, p = 0.017) had improved significantly. The stress-induced ischemia score within the injected territories (118 segments) had also improved (2.2 +/- 0.8 vs 1.7 +/- 1.1, p < 0.001). At 1 year, the clinical improvement was sustained, although 5 patients had undergone revascularization procedures. The number of total injected nucleated cells (CD45+), progenitor cells (CD34+), and the magnitude of secreted vascular endothelial growth factor and macrophage chemoattractant protein-1 by cultured BM cells failed to predict the clinical response. In conclusion, the 3- and 12-month study results have indicated the safety of catheter-based transendocardial delivery of autologous BM cells in patients with advanced symptomatic ischemic heart disease and may suggest sustained potential efficacy. The cellular and humeral characteristics of autologous BM cells did not predict the clinical response, underscoring the advisability of additional mechanistic exploration.
本报告包含一项I期研究的最终结果，该研究评估了在难治性心绞痛和心肌缺血的“无其他选择”患者中进行心肌内注射自体骨髓（BM）的可行性、安全性和潜在疗效。27例患者接受了在电机械标测引导下经心内膜向缺血、非梗死心肌区域注射（n = 12，每次0.2 ml）未分级的自体BM细胞。患者注射了每毫升含2.2±1.4% CD34+细胞的28±27×10⁶个有核细胞。自体BM注射程序在所有患者中均成功，且未出现不良事件。3个月时，加拿大心血管学会心绞痛评分（3.2±0.5对2.0±0.91，p = 0.001）和跑步机运动持续时间（418±136对489±142秒，p = 0.017）有显著改善。注射区域内（118个节段）的应激诱导缺血评分也有所改善（2.2±0.8对1.7±1.1，p < 0.001）。1年时，尽管有5例患者接受了血运重建手术，但临床改善得以维持。注射的有核细胞总数（CD45+）、祖细胞（CD34+）以及培养的BM细胞分泌的血管内皮生长因子和巨噬细胞趋化蛋白-1的量未能预测临床反应。总之，3个月和12个月的研究结果表明，在有症状的晚期缺血性心脏病患者中，经心内膜导管输送自体BM细胞是安全的，并且可能提示有持续的潜在疗效。自体BM细胞的细胞和体液特征未能预测临床反应，这突出了进一步进行机制探索的必要性。
