Department of Neurobiology, Harvard Medical School, Boston, Massachusetts, United States of America.
PLoS One. 2013 Jun 6;8(6):e65974. doi: 10.1371/journal.pone.0065974. Print 2013.
Neural stem cells (NSCs) are undifferentiated cells in the central nervous system (CNS) that are capable of self-renewal and can be induced to differentiate into neurons and glia. Current sources of mammalian NSCs are confined to regions of the CNS that are critical to normal function and surgically difficult to access, which limits their therapeutic potential in human disease. We have found that the filum terminale (FT), a previously unexplored, expendable, and easily accessible tissue at the caudal end of the spinal cord, is a source of multipotent cells in postnatal rats and humans. In this study, we used a rat model to isolate and characterize the potential of these cells. Neurospheres derived from the rat FT are amenable to in vitro expansion in the presence of a combination of growth factors. These proliferating, FT-derived cells formed neurospheres that could be induced to differentiate into neural progenitor cells, neurons, astrocytes, and oligodendrocytes by exposure to serum and/or adhesive substrates. Through directed differentiation using sonic hedgehog and retinoic acid in combination with various neurotrophic factors, FT-derived neurospheres generated motor neurons that were capable of forming neuromuscular junctions in vitro. In addition, FT-derived progenitors that were injected into chick embryos survived and could differentiate into both neurons and glia in vivo.
神经干细胞(NSCs)是中枢神经系统(CNS)中的未分化细胞,能够自我更新,并可被诱导分化为神经元和神经胶质细胞。目前哺乳动物 NSCs 的来源仅限于对正常功能至关重要且手术难以触及的 CNS 区域,这限制了它们在人类疾病中的治疗潜力。我们发现,脊髓末端的终丝(FT)是脊髓末端以前未被探索过的、可消耗的、易于接近的组织,是出生后大鼠和人类多能细胞的来源。在这项研究中,我们使用大鼠模型来分离和表征这些细胞的潜力。从大鼠 FT 中分离得到的神经球在生长因子组合的存在下可进行体外扩增。这些增殖的、FT 来源的细胞形成神经球,通过暴露于血清和/或粘附底物可诱导其分化为神经祖细胞、神经元、星形胶质细胞和少突胶质细胞。通过使用 sonic hedgehog 和视黄酸与各种神经营养因子的定向分化,FT 来源的神经球生成了能够在体外形成神经肌肉接头的运动神经元。此外,注入鸡胚的 FT 来源祖细胞存活下来,并能在体内分化为神经元和神经胶质细胞。