Department of Medicine, Surgery and Dentistry, Faculty of Medicine, University of Milan Via A. di Rudinì 8, 20142 Milan, Italy.
Exp Neurol. 2010 Jun;223(2):452-63. doi: 10.1016/j.expneurol.2010.01.010. Epub 2010 Jan 25.
The purpose of this study was to determine the fate and the effects of undifferentiated embryonic stem cells (ESCs) in mice after contusive lesion of the spinal cord (SCI). Reproducible traumatic lesion to the cord was performed at T8 level by means of the Infinite Horizon Device, and was followed by intravenous injection of one million of undifferentiated ESCs through the tail vein within 2 h from the lesion. The ESCs-treated animals showed a significant improvement of the recovery of motor function 28 days after lesion, with an average score of 4.61+/-0.13 points of the Basso Mouse Scale (n=14), when compared to the average score of vehicle treated mice, 3.58+/-0.23 (n=10). The number of identified ESCs found at the lesion site was 0.6% of the injected cells at 1 week after transplantation, and further reduced to 0.04% at 1 month. It is, thus, apparent that the promoted hind-limb recovery cannot be correlated to a substitution of the lost tissue performed by the exogenous ESC. The extensive evaluation of production of several neuroprotective and inflammatory cytokines did not reveal any effect by ESC-treatment, but unexpectedly the number of invading macrophages and neutrophils was greatly reduced. This may explain the improved preservation of lesion site ventral myelin, at both 1 week (29+/-11%) and 1 month (106+/-14%) after injury. No teratoma formation was observed, although an inappropriate colonization of the sacral cord by differentiated nestin- and beta-tubulin III-positive ESCs was detected.
本研究旨在确定未分化胚胎干细胞（ESCs）在脊髓损伤（SCI）后小鼠体内的命运和作用。通过无限地平线装置（Infinite Horizon Device）在 T8 水平上进行可复制的创伤性损伤，然后在损伤后 2 小时内通过尾静脉注射 100 万个未分化的 ESCs。与 vehicle 处理的小鼠相比，接受 ESCs 治疗的动物在损伤后 28 天运动功能恢复明显改善，平均 Basso 小鼠评分（Basso Mouse Scale）为 4.61+/-0.13 分（n=14），而接受 vehicle 处理的小鼠平均评分为 3.58+/-0.23 分（n=10）。移植后 1 周，在损伤部位发现的鉴定为 ESCs 的细胞数量为注射细胞的 0.6%，1 个月时进一步减少至 0.04%。因此，促进后肢恢复的作用不能与外源性 ESC 替代丢失组织相关联。对几种神经保护和炎症细胞因子的广泛评估并未发现 ESC 治疗的任何作用，但出人意料的是，入侵的巨噬细胞和中性粒细胞的数量大大减少。这可能解释了损伤后 1 周（29+/-11%）和 1 个月（106+/-14%）时损伤部位腹侧髓鞘的保存得到改善。虽然检测到分化的巢蛋白和β-微管蛋白 III 阳性的 ESCs 不恰当地定植于骶髓，但未观察到畸胎瘤形成。
