Emerich D F, McDermott P E, Krueger P M, Frydel B, Sanberg P R, Winn S R
Cyto Therapeutics, Inc. Providence, Rhode Island 02906.
Exp Neurol. 1993 Jul;122(1):37-47. doi: 10.1006/exnr.1993.1105.
The feasibility of using polymer-encapsulated PC12 cells to ameliorate the motor deficits in aged rats was evaluated. Spontaneous locomotion and motor coordination was evaluated in young (5-6 month) and aged (24-25 month) rats. Aged animals tested for spontaneous locomotor activity in Digiscan animal activity monitors were found to be hypoactive relative to young animals. Compared to the young animals the aged animals: (1) remained suspended from a horizontal wire for less time, (2) were unable to descend a wooden pole covered with wire mesh in a coordinated manner, (3) fell more rapidly from a rotating rod, and (4) were unable to maintain their balance on a series of wooden beams with either a square or rounded top of varying widths. Prior to implantation PC12 cell-loaded capsules were chromatographically characterized for catecholamine release. Following baseline testing, aged animals received either no implant, empty capsules, or PC12 cell-loaded capsules implanted bilaterally into the striatum. Three weeks following surgery, animals were retested and a significant improvement in balance on the rotorod and wooden beams was observed in those aged animals receiving PC12 cell-loaded capsules. No recovery was observed in the animals receiving PC12 cell-loaded capsules on any of the other motor tasks. Likewise, no improvement was observed on any behavioral measure in those animals receiving empty capsules. Histological analysis revealed the presence of numerous surviving tyrosine hydroxylase-positive PC12 cells within the capsules. Encapsulated PC12 cells survive following implantation into aged rats and such a technique may be useful for treating some of the behavioral consequences of aging.
评估了使用聚合物包裹的PC12细胞改善老年大鼠运动功能障碍的可行性。对年轻(5 - 6个月)和老年(24 - 25个月)大鼠的自发运动和运动协调性进行了评估。在Digiscan动物活动监测仪中测试自发运动活动时,发现老年动物相对于年轻动物活动不足。与年轻动物相比,老年动物:(1)在水平金属丝上悬挂的时间更短,(2)无法以协调的方式从覆盖有金属网的木杆上下来,(3)从旋转杆上掉落得更快,(4)在一系列顶部为方形或圆形、宽度各异的木梁上无法保持平衡。在植入前,对装载PC12细胞的胶囊进行了色谱分析以确定儿茶酚胺的释放情况。在基线测试后,老年动物双侧纹状体要么不植入、植入空胶囊,要么植入装载PC12细胞的胶囊。手术后三周,对动物进行重新测试,发现接受装载PC12细胞胶囊的老年动物在转子杆和木梁上的平衡有显著改善。在接受装载PC12细胞胶囊的动物的任何其他运动任务中均未观察到恢复情况。同样,接受空胶囊的动物在任何行为指标上均未观察到改善。组织学分析显示胶囊内存在大量存活的酪氨酸羟化酶阳性PC12细胞。包裹的PC12细胞在植入老年大鼠后能够存活,这种技术可能有助于治疗衰老的一些行为后果。