Windrem Martha S, Schanz Steven J, Guo Min, Tian Guo-Feng, Washco Vaughn, Stanwood Nancy, Rasband Matthew, Roy Neeta S, Nedergaard Maiken, Havton Leif A, Wang Su, Goldman Steven A
Department of Neurology, University of Rochester Medical Center, Rochester, NY 14642, USA.
Cell Stem Cell. 2008 Jun 5;2(6):553-65. doi: 10.1016/j.stem.2008.03.020.
Congenitally hypomyelinated shiverer mice fail to generate compact myelin and die by 18-21 weeks of age. Using multifocal anterior and posterior fossa delivery of sorted fetal human glial progenitor cells into neonatal shiverer x rag2(-/-) mice, we achieved whole neuraxis myelination of the engrafted hosts, which in a significant fraction of cases rescued this otherwise lethal phenotype. The transplanted mice exhibited greatly prolonged survival with progressive resolution of their neurological deficits. Substantial myelination in multiple regions was accompanied by the acquisition of normal nodes of Ranvier and transcallosal conduction velocities, ultrastructurally normal and complete myelination of most axons, and a restoration of a substantially normal neurological phenotype. Notably, the resultant mice were cerebral chimeras, with murine gray matter but a predominantly human white matter glial composition. These data demonstrate that the neonatal transplantation of human glial progenitor cells can effectively treat disorders of congenital and perinatal hypomyelination.
先天性髓鞘形成不足的颤抖小鼠无法生成致密髓鞘，在18 - 21周龄时死亡。通过将分选的胎儿人神经胶质祖细胞多灶性地注入新生颤抖小鼠x rag2(-/-)小鼠的前、后颅窝，我们实现了移植宿主整个神经轴的髓鞘形成，在很大一部分病例中挽救了这种原本致命的表型。移植小鼠的存活时间大大延长，神经功能缺陷逐渐得到缓解。多个区域的大量髓鞘形成伴随着正常郎飞结的获得和胼胝体传导速度的恢复，大多数轴突的超微结构正常且完全髓鞘化，以及基本正常神经表型的恢复。值得注意的是，所得小鼠是脑嵌合体，具有鼠灰质，但主要是人类白质神经胶质组成。这些数据表明，人神经胶质祖细胞的新生儿移植可以有效治疗先天性和围产期髓鞘形成不足的疾病。
