Unit of Physiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland.
Neurosurgery. 2011 May;68(5):1405-16; discussion 1416-7. doi: 10.1227/NEU.0b013e31820c02c0.
Although cell therapy is a promising approach after cerebral cortex lesion, few studies assess quantitatively its behavioral gain in nonhuman primates. Furthermore, implantations of fetal grafts of exogenous stem cells are limited by safety and ethical issues.
To test in nonhuman primates the transplantation of autologous adult neural progenitor cortical cells with assessment of functional outcome.
Seven adult macaque monkeys were trained to perform a manual dexterity task, before the hand representation in motor cortex was chemically lesioned unilaterally. Five monkeys were used as control, compared with 2 monkeys subjected to different autologous cells transplantation protocols performed at different time intervals.
After lesion, there was a complete loss of manual dexterity in the contralesional hand. The 5 "control" monkeys recovered progressively and spontaneously part of their manual dexterity, reaching a unique and definitive plateau of recovery, ranging from 38% to 98% of prelesion score after 10 to 120 days. The 2 "treated" monkeys reached a first spontaneous recovery plateau at about 25 and 40 days postlesion, representing 35% and 61% of the prelesion performance, respectively. In contrast to the controls, a second recovery plateau took place 2 to 3 months after cell transplantation, corresponding to an additional enhancement of functional recovery, representing 24% and 37% improvement, respectively.
These pilot data, derived from 2 monkeys treated differently, suggest that, in the present experimental conditions, autologous adult brain progenitor cell transplantation in a nonhuman primate is safe and promotes enhancement of functional recovery.
尽管细胞疗法是脑皮质损伤后的一种很有前途的治疗方法,但很少有研究对其在非人类灵长类动物中的行为增益进行定量评估。此外,外源性干细胞的胎儿移植存在安全性和伦理问题。
在非人类灵长类动物中测试自体成体神经祖细胞移植,并评估其功能结果。
7 只成年猕猴接受了一项手部灵巧性任务的训练,然后在单侧运动皮质进行化学性单侧损伤。其中 5 只猴子作为对照组,与 2 只猴子进行比较,这 2 只猴子分别接受了不同的自体细胞移植方案,时间间隔不同。
损伤后,对侧手部的手部灵巧性完全丧失。5 只“对照组”猴子逐渐自发地恢复了部分手部灵巧性,达到了一个独特且稳定的恢复平台,恢复幅度在损伤后 10 至 120 天内为术前评分的 38%至 98%。2 只“治疗”组猴子在损伤后约 25 天和 40 天达到第一次自发恢复平台,分别代表术前表现的 35%和 61%。与对照组不同的是,在细胞移植后 2 至 3 个月出现了第二次恢复平台,这对应着功能恢复的额外增强,分别提高了 24%和 37%。
这些来自 2 只接受不同治疗的猴子的初步数据表明,在本实验条件下,自体成体脑祖细胞移植在非人类灵长类动物中是安全的,并促进了功能恢复的增强。