Department of Physiology, Keio University School of Medicine, Shinjuku, Tokyo, Japan.
J Neurosci Res. 2010 May 15;88(7):1394-405. doi: 10.1002/jnr.22322.
Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI.
将神经干细胞/祖细胞(NS/PCs)延迟移植到损伤的脊髓中可以促进成年大鼠和猴子的功能恢复。为了增强 NS/PC 移植后的功能恢复,我们专注于半乳糖凝集素-1,这是一种具有细胞生长、分化、凋亡和神经突生长等多种作用的碳水化合物结合蛋白。在这里,为了确定 NS/PC 移植和半乳糖凝集素-1联合治疗脊髓损伤(SCI)的效果,我们通过慢病毒将半乳糖凝集素-1和绿色荧光蛋白(GFP)转染到人类 NS/PC 中,(Gal-NS/PCs)或单独转染 GFP(GFP-NS/PCs),在体外扩增,然后在挫伤性颈 SCI 后 9 天移植到成年普通狨猴的脊髓中。通过动物的自发运动活动、棒抓握力和在跑步机测试上的表现来评估其运动功能。组织学分析显示,移植的人类 NS/PCs 存活并分化为神经元、星形胶质细胞和少突胶质细胞。Gal-NS/PC、GFP-NS/PC、载体对照和假手术组之间的有髓面积、皮质脊髓纤维和 5-羟色胺能纤维存在显著差异。与其他组相比,Gal-NS/PC 移植组的动物在所有行为测试中表现更好。这些发现表明,Gal-NS/PC 比 NS/PC 对非人类灵长类动物的 SCI 具有更好的治疗潜力,并且人类 Gal-NS/PC 移植可能是治疗人类 SCI 的一种可行方法。