Kopen G C, Prockop D J, Phinney D G
Center for Gene Therapy, MCP Hahnemann University, 245 North 15th Street, Philadelphia, PA 19102-1192, USA.
Proc Natl Acad Sci U S A. 1999 Sep 14;96(19):10711-6. doi: 10.1073/pnas.96.19.10711.
Stem cells are a valuable resource for treating disease, but limited access to stem cells from tissues such as brain restricts their utility. Here, we injected marrow stromal cells (MSCs) into the lateral ventricle of neonatal mice and asked whether these multipotential mesenchymal progenitors from bone marrow can adopt neural cell fates when exposed to the brain microenvironment. By 12 days postinjection, MSCs migrated throughout the forebrain and cerebellum without disruption to the host brain architecture. Some MSCs within the striatum and the molecular layer of the hippocampus expressed glial fibrillary acidic protein and, therefore, differentiated into mature astrocytes. MSCs also populated neuron rich regions including the Islands of Calleja, the olfactory bulb, and the internal granular layer of the cerebellum. A large number of MSCs also were found within the external granular layer of the cerebellum. In addition, neurofilament positive donor cells were found within the reticular formation of the brain stem, suggesting that MSCs also may have differentiated into neurons. Therefore, MSCs are capable of producing differentiated progeny of a different dermal origin after implantation into neonatal mouse brains. These results suggest that MSCs are potentially useful as vectors for treating a variety of central nervous system disorders.
干细胞是治疗疾病的宝贵资源,但从诸如脑等组织获取干细胞的途径有限,这限制了它们的效用。在此,我们将骨髓基质细胞(MSCs)注入新生小鼠的侧脑室,并探究当暴露于脑微环境时,这些来自骨髓的多能间充质祖细胞是否能够转变为神经细胞命运。注射后12天,MSCs迁移至整个前脑和小脑,而未破坏宿主脑结构。纹状体和海马分子层内的一些MSCs表达胶质纤维酸性蛋白,因此分化为成熟星形胶质细胞。MSCs也分布于富含神经元的区域,包括Calleja岛、嗅球和小脑内颗粒层。在小脑外颗粒层也发现大量MSCs。此外,在脑干网状结构内发现神经丝阳性供体细胞,提示MSCs也可能已分化为神经元。因此,MSCs植入新生小鼠脑内后能够产生不同真皮来源的分化后代。这些结果表明,MSCs作为治疗多种中枢神经系统疾病的载体具有潜在用途。