Cummings Brian J, Uchida Nobuko, Tamaki Stanley J, Salazar Desirée L, Hooshmand Mitra, Summers Robert, Gage Fred H, Anderson Aileen J
Department of Physical Medicine and Rehabilitation, Reeve-Irvine Research Center, University of California, Irvine, CA 92697, USA.
Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):14069-74. doi: 10.1073/pnas.0507063102. Epub 2005 Sep 19.
We report that prospectively isolated, human CNS stem cells grown as neurospheres (hCNS-SCns) survive, migrate, and express differentiation markers for neurons and oligodendrocytes after long-term engraftment in spinal cord-injured NOD-scid mice. hCNS-SCns engraftment was associated with locomotor recovery, an observation that was abolished by selective ablation of engrafted cells by diphtheria toxin. Remyelination by hCNS-SCns was found in both the spinal cord injury NOD-scid model and myelin-deficient shiverer mice. Moreover, electron microscopic evidence consistent with synapse formation between hCNS-SCns and mouse host neurons was observed. Glial fibrillary acidic protein-positive astrocytic differentiation was rare, and hCNS-SCns did not appear to contribute to the scar. These data suggest that hCNS-SCns may possess therapeutic potential for CNS injury and disease.
我们报告称,前瞻性分离的、以神经球形式生长的人中枢神经系统干细胞(hCNS-SCns)在长期植入脊髓损伤的NOD-scid小鼠后能够存活、迁移并表达神经元和少突胶质细胞的分化标志物。hCNS-SCns的植入与运动功能恢复相关,白喉毒素选择性消融植入细胞可消除这一观察结果。在脊髓损伤的NOD-scid模型和髓鞘缺乏的颤抖小鼠中均发现hCNS-SCns参与了髓鞘再生。此外,观察到了与hCNS-SCns和小鼠宿主神经元之间突触形成一致的电子显微镜证据。胶质纤维酸性蛋白阳性的星形胶质细胞分化很少见,hCNS-SCns似乎对瘢痕形成没有贡献。这些数据表明,hCNS-SCns可能对中枢神经系统损伤和疾病具有治疗潜力。