Oka Shinichi, Honmou Osamu, Akiyama Yukinori, Sasaki Masanori, Houkin Kiyohiro, Hashi Kazuo, Kocsis Jeffery D
Department of Neurosurgery, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8543, Japan.
Brain Res. 2004 Dec 24;1030(1):94-102. doi: 10.1016/j.brainres.2004.09.062.
The objective of this study was to establish if neural precursor cells could safely be developed from biopsy of the subventricular zone (SVZ) in the non-human primate (marmoset), and to determine their myelinating potential after autologous transplantation into a demyelinated lesion. Small amounts of tissue were safely collected from the subventricular-subependymal zone of the adult primate brain under ultrasonography without any neurological deficit. Neural precursor cells were isolated and expanded in the presence of mitogen in vitro. The dorsal columns of the adult marmoset spinal cord were demyelinated by X-irradiation and intraspinal injections of ethidium bromide in the center of the radiation field. Cell suspensions of the neural precursors were microinjected through a micropipette into the demyelinated lesion site in the spinal cord. Lesions were histologically examined 3 weeks after transplantation. Light and electron microscopic examination of plastic embedded sections revealed a significant number of myelinating profiles in the transplantation zone; no myelination was observed in control lesions. The myelinated axons had predominantly peripheral patterns of myelination. These results demonstrate that autologous transplantation of neural precursor cells in the adult nonhuman primate can remyelinate demyelinated central nervous system (CNS) axons, thus suggesting the potential utility of such an approach in demyelinating lesions in humans.
本研究的目的是确定能否从非人灵长类动物(狨猴)脑室下区(SVZ)活检组织中安全地培养出神经前体细胞,并确定将其自体移植到脱髓鞘损伤部位后它们的髓鞘形成潜力。在超声引导下,从成年灵长类动物大脑的脑室下-室管膜下区安全采集少量组织,未出现任何神经功能缺损。在有丝分裂原存在的情况下,体外分离并扩增神经前体细胞。通过X射线照射和在辐射野中心脊髓内注射溴化乙锭,使成年狨猴脊髓的背柱脱髓鞘。将神经前体细胞悬液通过微量移液器微量注射到脊髓脱髓鞘损伤部位。移植3周后对损伤部位进行组织学检查。对塑料包埋切片进行光镜和电镜检查发现,移植区有大量髓鞘形成的图像;对照损伤部位未观察到髓鞘形成。髓鞘化的轴突主要呈外周髓鞘形成模式。这些结果表明,成年非人灵长类动物自体移植神经前体细胞可使脱髓鞘的中枢神经系统(CNS)轴突重新髓鞘化,因此提示这种方法在人类脱髓鞘损伤中的潜在应用价值。