Mitra Siddhartha S, Feroze Abdullah H, Gholamin Sharareh, Richard Chase, Esparza Rogelio, Zhang Michael, Azad Tej D, Alrfaei Bahaudeen, Kahn Suzana A, Hutter Gregor, Guzman Raphael, Creasey Graham H, Plant Giles W, Weissman Irving L, Edwards Michael S B, Cheshier Samuel
‡Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California; §Department of Neurosurgery, Lucile Packard Children's Hospital, Stanford University School of Medicine, Stanford, California; ¶Department of Neurosurgery, VA Palo Alto Health Care System, Stanford University School of Medicine, Palo Alto, California; ∥Department of Neurological Surgery, University of Washington, Seattle, Washington.
Neurosurgery. 2015 Nov;77(5):794-802; discussion 802. doi: 10.1227/NEU.0000000000000918.
The presence, characteristics, and potential clinical relevance of neural progenitor populations within the neural placodes of myelomeningocele patients remain to be studied. Neural stem cells are known to reside adjacent to ependyma-lined surfaces along the central nervous system axis.
Given such neuroanatomic correlation and regenerative capacity in fetal development, we assessed myelomeningocele-derived neural placode tissue as a potentially novel source of neural stem and progenitor cells.
Nonfunctional neural placode tissue was harvested from infants during the surgical repair of myelomeningocele and subsequently further analyzed by in vitro studies, flow cytometry, and immunofluorescence. To assess lineage potential, neural placode-derived neurospheres were subjected to differential media conditions. Through assessment of platelet-derived growth factor receptor α (PDGFRα) and CD15 cell marker expression, Sox2+Olig2+ putative oligodendrocyte progenitor cells were successfully isolated.
PDGFRαCD15 cell populations demonstrated the highest rate of self-renewal capacity and multipotency of cell progeny. Immunofluorescence of neural placode-derived neurospheres demonstrated preferential expression of the oligodendrocyte progenitor marker, CNPase, whereas differentiation to neurons and astrocytes was also noted, albeit to a limited degree.
Neural placode tissue contains multipotent progenitors that are preferentially biased toward oligodendrocyte progenitor cell differentiation and presents a novel source of such cells for use in the treatment of a variety of pediatric and adult neurological disease, including spinal cord injury, multiple sclerosis, and metabolic leukoencephalopathies.
脊髓脊膜膨出患者神经板内神经祖细胞群的存在、特征及潜在临床相关性仍有待研究。已知神经干细胞沿中枢神经系统轴位于室管膜衬里表面附近。
鉴于胎儿发育中的这种神经解剖学关联和再生能力,我们评估了脊髓脊膜膨出衍生的神经板组织作为神经干细胞和祖细胞的潜在新来源。
在脊髓脊膜膨出手术修复过程中从婴儿身上采集无功能的神经板组织,随后通过体外研究、流式细胞术和免疫荧光进行进一步分析。为了评估谱系潜能,将神经板衍生的神经球置于不同的培养基条件下。通过评估血小板衍生生长因子受体α(PDGFRα)和CD15细胞标志物表达,成功分离出Sox2 + Olig2 +假定少突胶质细胞祖细胞。
PDGFRαCD15细胞群体表现出最高的自我更新能力和细胞后代的多能性。神经板衍生神经球的免疫荧光显示少突胶质细胞祖细胞标志物CNPase的优先表达,同时也观察到向神经元和星形胶质细胞的分化,尽管程度有限。
神经板组织含有多能祖细胞,这些祖细胞优先倾向于少突胶质细胞祖细胞分化,并为治疗包括脊髓损伤、多发性硬化症和代谢性白质脑病在内的各种儿科和成人神经系统疾病提供了此类细胞的新来源。