Joannides Alexis, Gaughwin Phil, Scott Mike, Watt Suzanne, Compston Alastair, Chandran Siddharthan
Cambridge Centre for Brain Repair and Department of Neurology, University of Cambridge, Cambridge CB2 2PY, UK.
J Hematother Stem Cell Res. 2003 Dec;12(6):681-8. doi: 10.1089/15258160360732704.
Neural stem cells (NSCs) have generated considerable interest because of their potential as a source of defined cells for drug screening or cell-based therapies for neurodegenerative diseases. Ethical and practical considerations limit the availability of human fetal-derived neural tissue and highlight the need to consider alternative sources of human NSCs. Because of their ready availability, their ability to be easily expanded, and reports of neural potential, bone marrow-derived populations have become the focus of intense study with regard to their potential clinical utility. However, recent identification of spontaneous cell fusion and limited neuronal differentiation has tempered initial optimism. In this study, we demonstrate the monoclonal neural and mesodermal potential of adult human bone marrow mesenchymal cells. Critically, we show that sequential treatment with the mitogens epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) followed by postnatal hippocampal astrocyte conditioned medium significantly promotes the generation of neurofilament(+)/beta-tubulin(+) cells from bone marrow precursors. The ability to generate almost limitless numbers of neural precursors from a readily accessible autologous adult human source provides a platform for further studies and potentially has important therapeutic implications.
神经干细胞(NSCs)因其作为用于药物筛选的特定细胞来源或神经退行性疾病基于细胞的治疗方法的潜力而引起了广泛关注。伦理和实际考虑限制了人类胎儿来源神经组织的可用性,并突出了考虑人类神经干细胞替代来源的必要性。由于其易于获取、易于扩增的能力以及神经潜能的报道,骨髓来源的细胞群体已成为其潜在临床应用的深入研究焦点。然而,最近对自发细胞融合和有限神经元分化的鉴定削弱了最初的乐观情绪。在本研究中,我们证明了成人骨髓间充质细胞的单克隆神经和中胚层潜能。至关重要的是,我们表明,先用有丝分裂原表皮生长因子(EGF)和成纤维细胞生长因子-2(FGF-2)进行序贯处理,然后用出生后海马星形胶质细胞条件培养基处理,可显著促进骨髓前体细胞产生神经丝(+)/β-微管蛋白(+)细胞。从易于获取的自体成人来源产生几乎无限数量的神经前体细胞的能力为进一步研究提供了一个平台,并可能具有重要的治疗意义。