Evaluation of surgical techniques for neuronal cell transplantation used in patients with stroke
Evaluation of surgical techniques for neuronal cell transplantation used in patients with stroke
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DOI：
10.3727/000000004783983350
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发表时间：
2004-01-01
影响因子：
3.3
通讯作者：
McGrogan, M
中科院分区：
文献类型：
--
作者：
Kondziolka, D;Steinberg, GK;McGrogan, M
在卒中动物模型中证明了培养的神经细胞的安全性和有效性后，进行了两项人体临床试验。这些研究测试了人类神经元细胞移植到小卒中体积内及其周围的效用。我们开发了一种立体定向手术技术用于细胞递送，并在26例基底神经节区运动中风患者中对该方法进行了评估。人神经元细胞（hNT细胞；LBS神经元）冷冻后解冻，于手术当天早晨配制。在第一次试验中，患者在3到9次植入中接受了200万到600万个细胞，在第二次试验中，患者在25次植入中接受了500万到1000万个细胞。一种新型的细胞输送管被设计、制造、测试并用于外科手术。术后立即CT扫描和随后的连续MR扫描用于评估手术部位。对细胞植入套管的测试表明，注射后细胞未受损，并保持活力。所有患者均进行了简单的手术。细胞可在2 h内植入，保持制剂的活力。连续评估（最长5年）显示没有细胞相关的不良血清学或影像学影响。1例无症状慢性硬膜下血肿采用钻孔引流术。人类神经元细胞可以在培养中产生，并以立体定向的方式植入中风患者的大脑中。手术细胞递送没有导致新的神经功能缺损，影像学研究显示没有不良反应。所使用的导管允许在维持细胞活力的一段时间内精确注射临床细胞剂量。
Transplantation of cultured neuronal cells was performed in two human clinical trials after safety and efficacy was demonstrated in animal models of stroke. The studies tested the utility of human neuronal cellular transplantation into and around the small stroke volume. We developed a stereotactic surgical technique for cell delivery and evaluated that method in 26 patients with basal ganglia region motor stroke. Human neuronal cells (hNT cells; LBS neurons) were delivered frozen then thawed and formulated on the morning of surgery. Patients in a first trial received 2 or 6 million cells in three or nine implants, and in a second trial, 5 or 10 million in 25 implants. A novel cell delivery cannula was designed, manufactured, tested, and used in surgery. Immediate postoperative CT scans and later serial MR scans were used to evaluate the surgical site. Tests on the cell implantation cannula showed that the cells were not damaged and remained viable after injection. All patients underwent uncomplicated surgeries. Cells could be implanted within a 2-h period, maintaining viability of the preparation. Serial evaluations (maximum 5 years) showed no cell-related adverse serologic or imaging-defined effects. One patient had burr hole drainage of an asymptomatic chronic subdural hematoma. Human neuronal cells can be produced in culture and implanted stereotactically into the brains of patients with stroke. Surgical cell delivery did not lead to new neurological deficits, and imaging studies showed no adverse effects. The cannula used allowed precise injection of the clinical cell dose within a time period that maintained cell viability.