Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: Phase I study results
Clinical experience using incubated autologous macrophages as a treatment for complete spinal cord injury: Phase I study results
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DOI：
10.3171/spi.2005.3.3.0173
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发表时间：
2005-09-01
影响因子：
2.8
通讯作者：
Hadani, M
中科院分区：
文献类型：
--
作者：
Knoller, N;Auerbach, G;Hadani, M
目的。进行了一项 I 期开放标签非随机研究，以评估给予急性完全性脊髓损伤 (SCI) 患者的孵化自体巨噬细胞的安全性和耐受性。方法。这种疗法首先在脊髓横断和挫伤的大鼠模型中进行了测试，结果显示它可以促进运动恢复。为临床使用而开发的程序包括从患者血液中分离单核细胞并将其与自体真皮离体孵育。在受伤后 14 天内，将所得孵化的自体巨噬细胞注射到患者病变部位尾部的脊髓中。患者接受术前和随访神经学评估（美国脊柱损伤协会[ASIA]标准）、电生理监测（运动诱发和/或体感诱发电位）、磁共振成像和安全监测。在巨噬细胞给药之前，所有患者均确认神经功能完全丧失（ASIA A 级）。在该研究的 8 名患者中，3 名患者恢复了具有临床意义的神经运动和感觉功能（ASIA C 级状态）。在研究期间，遇到了一些不良事件，其中最严重的是两例肺栓塞和一例骨髓炎，经过治疗和解决，没有出现进一步的并发症。这些和其他不良事件似乎与其他脊髓损伤患者中遇到的不良事件相似，不被认为是实验治疗的结果。结论。结论是，急性 SCI 患者对培养的自体巨噬细胞疗法具有良好的耐受性。需要进一步的临床评估。
Object. A Phase I, open-label nonrandomized study was conducted to assess the safety and tolerability of incubated autologous macrophages administered to patients with acute complete spinal cord injury (SCI).Methods. This therapy was first tested in rat models of spinal cord transection and contusion, in which it was shown to promote motor recovery. The procedure developed for clinical use consists of isolating monocytes from patient blood and incubating them ex vivo with autologous dermis. The resulting incubated autologous macrophages were injected into the patient's spinal cord immediately caudal to the lesion within 14 days of injury. Patients underwent preoperative and follow-up neurological assessment (American Spinal Injury Association [ASIA] standards), electrophysiological monitoring (motor evoked and/or somatosensory evoked potentials), magnetic resonance imaging, and safety monitoring. Before macrophage administration, complete neurological functional loss (ASIA Grade A) was confirmed in all patients. Of the eight patients in the study, three recovered clinically significant neurological motor and sensory function (ASIA Grade C status). During the study period, some adverse events were encountered, the most serious of which involved two cases of pulmonary embolism and one case of osteomyelitis that were treated and resolved without further complication. These and other adverse events appear to be similar to those encountered in other spinal cord-injured patients and are not considered a consequence of the experimental therapy.Conclusions. It is concluded that incubated autologous macrophage cell therapy is well tolerated in patients with acute SCI. Further clinical evaluation is warranted.