Reeve-Irvine Research Center, University of California at Irvine School of Medicine, Irvine, CA 92697-4265, USA.
Exp Neurol. 2012 Feb;233(2):625-44. doi: 10.1016/j.expneurol.2010.12.020. Epub 2010 Dec 30.
This study was undertaken as part of the NIH "Facilities of Research-Spinal Cord Injury" project to support independent replication of published studies. Here, we repeated a study reporting that a combinatorial treatment with transplants of Schwann cells, systemic delivery of Rolipram to enhance cyclic AMP levels, and intra-spinal injections of dibutyryl cyclic AMP enhanced locomotor recovery in rats after contusion injuries at the thoracic level. We compared the following experimental groups: 1) rats that received Schwann cell transplants, systemic Rolipram, and injections of db-cyclic AMP (the combined treatment group that showed the greatest improvement in function); 2) rats that received Schwann cell transplants only and implantation of empty pumps as control; 3) rats that received Rolipram only and implantation of empty pumps as control, and 4) control rats that received no treatment other than the injection of DMEM into the spinal cord and implantation of empty pumps. The principal findings reported in Pearse et al. were not replicated in that the combined treatment group did not exhibit greater recovery on any of the measures, although the group that received Schwann cells only did exhibit enhanced recovery on several of the outcome measures. The failure of the combined treatment may be due in part to less successful engraftment of Schwann cells in our study vs. Pearse et al. Issues relating to failures to replicate, especially when effect size is small, are discussed.
这项研究是 NIH“脊髓损伤研究设施”项目的一部分,旨在支持已发表研究的独立复制。在这里,我们重复了一项研究,该研究报告称,联合应用雪旺细胞移植、全身性给予罗利普兰以提高环磷酸腺苷水平,以及鞘内注射二丁酰环磷酸腺苷,可增强大鼠胸段挫伤后运动功能的恢复。我们比较了以下实验组:1)接受雪旺细胞移植、全身性罗利普兰和鞘内注射 db-cAMP(显示功能改善最大的联合治疗组)的大鼠;2)仅接受雪旺细胞移植和空泵植入作为对照的大鼠;3)仅接受罗利普兰和空泵植入作为对照的大鼠,以及 4)除了向脊髓内注射 DMEM 和植入空泵外,未接受其他治疗的对照大鼠。Pearse 等人报告的主要发现未被复制,即联合治疗组在任何测量指标上均未表现出更大的恢复,尽管仅接受雪旺细胞的组在几个结果测量指标上表现出增强的恢复。联合治疗的失败可能部分归因于我们的研究中雪旺细胞的植入不如 Pearse 等人成功。讨论了与未能复制相关的问题,特别是当效果大小较小时。