Zhang GuangZhu, Cunningham Miles, Zhang HongTian, Dai YiWu, Zhang Ping, Ge GuangZhi, Wang BeiBei, Bai MiaoChun, Hazel Thomas, Johe Karl, Xu RuXiang
Affiliated BaYi Brain Hospital, Army General Hospital of PLA, Beijing, China.
Laboratory for Neural Reconstruction, McLean Hospital, Harvard Medical School, Belmont, Massachusetts.
Oper Neurosurg. 2020 May 1;18(5):503-510. doi: 10.1093/ons/opz204.
In preclinical studies, the Intracerebral Microinjection Instrument (IMI) has demonstrated the ability to deliver therapeutics within the brain in 3-dimensional arrays from a single overlying penetration while incurring minimal localized trauma.
To evaluate the safety and performance of the IMI in its first use in humans to deliver stem cells in complex configurations within brain regions affected by ischemic injury.
As part of a phase 1 study, 3 chronically hemiparetic motor stroke patients received intracerebral grafts of the therapeutic stem cell line, NSI-566, using the IMI and its supporting surgical planning software. The patients were 37 to 54 yr old, had ischemic strokes more than 1 yr prior to transplantation, and received Fugl-Meyer motor scale scores of 17-48 at screening. During a single surgical procedure, patients received several neural grafts (42 ± 3) within the peri-infarct region targeted strategically to facilitate neural repair.
The IMI enabled multiple cellular deposits to be safely placed peripheral to stroke lesions. The procedure was well tolerated, recovery was uneventful, and there occurred no subsequent complications. The IMI performed reliably throughout the procedures without evident targeting errors. One year after transplantation, all 3 subjects displayed significant clinical improvement, and imaging analysis demonstrated occupation of infarct cavities with new tissue without tumor formation.
IMI technology permits unprecedented numbers of injections to be tactically placed in 3-dimensional arrays safely and reliably in human subjects.This advanced methodology can optimize the benefits of novel therapeutics by enabling versatile 3-dimensional intracerebral targeting.
在临床前研究中，脑内微注射仪器（IMI）已证明能够通过单次覆盖穿透以三维阵列形式在脑内递送治疗药物，同时使局部创伤最小化。
评估IMI首次用于人类，在受缺血性损伤影响的脑区域以复杂配置递送干细胞时的安全性和性能。
作为1期研究的一部分，3例慢性偏瘫性运动卒中患者使用IMI及其配套的手术规划软件接受了治疗性干细胞系NSI-566的脑内移植。患者年龄在37至54岁之间，在移植前1年以上发生缺血性卒中，筛查时Fugl-Meyer运动量表评分为17 - 48分。在单次手术过程中，患者在梗死灶周围区域接受了多个神经移植物（42±3个），这些移植物经过战略定位以促进神经修复。
IMI能够将多个细胞沉积物安全地放置在卒中病变周围。该手术耐受性良好，恢复顺利，且未出现后续并发症。IMI在整个手术过程中运行可靠，没有明显的靶向错误。移植1年后，所有3名受试者均显示出显著的临床改善，影像学分析显示梗死腔被新组织填充，无肿瘤形成。
IMI技术能够在人类受试者中安全可靠地以三维阵列形式战术性地放置前所未有的大量注射物。这种先进的方法可以通过实现通用的三维脑内靶向来优化新型治疗药物的疗效。
