CytoTherapeutics, Inc., 4 Richmond Square, Providence, RI 02906, USA.
Restor Neurol Neurosci. 1997 Jan 1;11(1):21-35. doi: 10.3233/RNN-1997-111203.
Numerous studies have reported that adrenal chromaffin cell transplants, including encapsulated xenogeneic adrenal chromaffin cells, have analgesic effects. However, in addition to efficacy, the clinical utility of encapsulated xenogeneic adrenal chromaffin cells for treatment of chronic pain is dependent on the duration of cell viability in vivo, and their relative safety. The objectives of the present study in rats were to: (1) examine encapsulated calf adrenal chromaffin (CAC) cells for evidence of viable cells and continued release of analgesic agents after an extended period in vivo; (2) determine if intraventricular encapsulated CAC cells produce detectable adverse effects on behavioral/cognitive function; and (3) test for evidence of host immune sensitization after an extended period of exposure to encapsulated xenogeneic adrenal chromaffin cells. Results of the present study suggest that some encapsulated CAC cells remain viable for nearly 1.5 years in vivo and continue to produce catecholamines and met-enkephalin. Post-explant device norepinephrine output was equivalent to amounts previously shown to produce analgesic effects with intrathecal implants. Encapsulated adrenal chromaffin cells also appeared relatively safe, even when implanted in the cerebral ventricals, with a lower side-effect profile than systemic morphine (4 mg/kg). There was no evidence that encapsulated CAC-cells implanted in the ventricles affected body weight, spontaneous activity levels, or performance in the delayed matching to position operant task which is sensitive to deficits in learning, memory, attention, motivation, and motor function. Finally, encapsulated CAC cells produced no detectable evidence of host immune sensitization after 16.7 months in vivo, although unencapsulated CAC cells produced a robust immune response even in aged rats. The results of the present study suggest that adrenal chromaffin cells remain viable in vivo for long periods of time, and that long-term exposure to encapsulated xenogeneic adrenal chromaffin cell implants appears relatively safe.
许多研究报告指出，肾上腺嗜铬细胞移植，包括包封的异种肾上腺嗜铬细胞，具有镇痛作用。然而，除了疗效外，用于治疗慢性疼痛的包封异种肾上腺嗜铬细胞的临床实用性还取决于细胞在体内的存活时间及其相对安全性。本研究的目的是在大鼠中：（1）检查包封的小牛肾上腺嗜铬细胞（CAC）细胞，以证明在体内延长时间后仍有存活细胞和持续释放镇痛剂；（2）确定脑室内包封的 CAC 细胞是否对行为/认知功能产生可检测的不良影响；（3）在长时间暴露于包封的异种肾上腺嗜铬细胞后，测试是否有宿主免疫致敏的证据。本研究结果表明，一些包封的 CAC 细胞在体内仍能存活近 1.5 年，并继续产生儿茶酚胺和 Met-脑啡肽。取出装置后的去甲肾上腺素输出量与先前通过鞘内植入物产生镇痛作用的量相当。即使植入脑室，包封的肾上腺嗜铬细胞也似乎相对安全，其副作用比全身吗啡（4mg/kg）小。没有证据表明植入脑室的包封 CAC 细胞会影响体重、自发活动水平或在延迟匹配位置操作任务中的表现，该任务对学习、记忆、注意力、动机和运动功能的缺陷敏感。最后，尽管未包封的 CAC 细胞即使在老年大鼠中也会引起强烈的免疫反应，但在体内 16.7 个月后，包封的 CAC 细胞未产生可检测到的宿主免疫致敏证据。本研究结果表明，肾上腺嗜铬细胞在体内能长时间存活，并且长期暴露于包封的异种肾上腺嗜铬细胞植入物似乎相对安全。
