Herrera J, Yang H, Zhang S C, Proschel C, Tresco P, Duncan I D, Luskin M, Mayer-Proschel M
Keck Center for Tissue Engineering, University of Utah, Salt Lake City, Utah.
Exp Neurol. 2001 Sep;171(1):11-21. doi: 10.1006/exnr.2001.7729.
We have isolated and characterized a unique glial-restricted precursor cell (GRP) from the embryonic spinal cord. Clonal analysis demonstrated that these cells are able to generate oligodendrocytes and two distinct type of astrocytes (type 1 and type 2) when exposed to appropriate signals in vitro. We now show that many aspects of these cells are retained in vivo. GRP cells are restricted to the glial lineage in vivo as they seem to be unable to generate neuronal phenotypes in an in vivo neurogenic environment. GRP cells survive and migrate in the neonatal and adult brain. Transplanted GRP cells differentiate into myelin-forming oligodendrocytes in a myelin-deficient background and also generate immature oligodendrocytes in the normal neonatal brain. In addition, GRP cells also consistently generated glial fibrillary protein-expressing cells in the neonatal and adult brain, a property not consistently expressed by other glial precursor cells like the O-2A/OPC cells. We suggest that the lineage restriction of GRP cells and their ability to generate both oligodendrocytes and astrocytes in vivo together with their embryonic character that allows for extensive in vitro expansion of the population makes the cell useful for clinical application.
我们从胚胎脊髓中分离并鉴定了一种独特的神经胶质限制性前体细胞（GRP）。克隆分析表明，这些细胞在体外暴露于适当信号时能够生成少突胶质细胞和两种不同类型的星形胶质细胞（1型和2型）。我们现在表明，这些细胞的许多特性在体内得以保留。GRP细胞在体内限于神经胶质谱系，因为它们似乎无法在体内神经发生环境中生成神经元表型。GRP细胞在新生和成年大脑中存活并迁移。移植的GRP细胞在髓鞘缺乏背景下分化为形成髓鞘的少突胶质细胞，并且在正常新生大脑中也生成未成熟的少突胶质细胞。此外，GRP细胞在新生和成年大脑中还持续生成表达胶质纤维酸性蛋白的细胞，这是其他神经胶质前体细胞如O-2A/少突胶质前体细胞不一致表达的特性。我们认为，GRP细胞的谱系限制及其在体内生成少突胶质细胞和星形胶质细胞的能力，以及其胚胎特性允许该细胞群体在体外大量扩增，使得该细胞在临床应用中具有实用性。
