Clinical Impact of Combined Transplantation of Autologous Skeletal Myoblasts and Bone Marrow Mononuclear Cells in Patients with Severely Deteriorated Ischemic Cardiomyopathy

Clinical Impact of Combined Transplantation of Autologous Skeletal Myoblasts and Bone Marrow Mononuclear Cells in Patients with Severely Deteriorated Ischemic Cardiomyopathy
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DOI:
10.1007/s00595-010-4526-3
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发表时间:
2011-08-01
期刊:
影响因子:
2.5
通讯作者:
Sawa, Yoshiki
Sawa, Yoshiki
中科院分区:
医学4区
文献类型:
--
作者:
Fujita, Tomoyuki;Sakaguchi, Taichi;Sawa, Yoshiki

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目的.同时注射自体骨髓细胞和骨骼肌成肌细胞已被证明可以改善动物模型的心脏功能。我们评估了这种联合细胞疗法在需要左心室辅助装置(LVAD)重建的严重缺血性心肌病患者中的潜在应用。研究了4例因严重缺血性心肌病需要植入LVAD的患者(年龄范围,43-69岁)。从大腿获得骨骼成肌细胞,而在手术时收集并纯化骨髓单核细胞。将这些细胞以连续的方式直接注射到受损的心肌中。未观察到致死性心律失常或严重并发症。注射的骨骼肌成肌细胞的数量范围为2.7 × 10(7)至3.0 × 10(8),其纯度范围为25%至96%。2例患者显示移植区域脑钠肽水平降低和超声心动图改善,以及(H2O)-O-15正电子发射断层扫描显示灌注增加,其中1例成功脱离LVAD。另一名患者尸检时的组织学结果显示,注射区域有少量骨骼肌。在另外两名患者中仅观察到轻微改善。联合细胞移植对严重缺血性心肌病患者是可行的,并且预期在选定的患者中功能恢复。
Purpose. Simultaneous injection of autologous bone marrow cells and skeletal myoblasts has been demonstrated to improve cardiac function in animal models. We evaluated the potential application of this combination cell therapy in patients with severe ischemic cardiomyopathy who required left ventricular assist device (LVAD) implantation.Methods. Four patients (age range, 43-69 years) who required LVAD implantation due to severe ischemic cardiomyopathy were studied. Skeletal myoblasts were obtained from the thigh, while bone marrow mononuclear cells were collected and purified at the time of the operation. These cells were directly injected in a serial manner into the damaged myocardium.Results. No fatal arrhythmias or major complications were observed. The number of injected skeletal myoblasts ranged from 2.7 x 10(7) to 3.0 x 10(8), and their purity ranged from 25% to 96%. Two patients showed decreased brain natriuretic peptide levels and echocardiographic improvements in the transplanted areas, as well as increased perfusion revealed by (H2O)-O-15 positron emission tomography, of whom one was successfully weaned from LVAD. Histological findings at autopsy of the other patient showed a small amount of skeletal muscle in the injected area. Only marginal improvements were observed in the other two patients.Conclusions. Combined cell transplantation is feasible for patients with severe ischemic cardiomyopathy, and functional recovery is anticipated in selected patients.