Transplanted CNS stem cells form functional synapses in vivo

Transplanted CNS stem cells form functional synapses in vivo
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DOI:
10.1046/j.1460-9568.2000.00067.x
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发表时间:
2000-05-01
影响因子:
3.4
通讯作者:
McKay, RDG
McKay, RDG
中科院分区:
医学3区
文献类型:
--
作者:
Auerbach, JM;Eiden, MV;McKay, RDG

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通过移植到神经系统中可以了解发育机制和新的细胞疗法。多能干细胞已从胎儿和成人中枢神经系统(CNS)中分离出来。永生化和初级前体细胞整合到发育中的大脑中,产生由免疫学和形态学标准定义的神经元和神经胶质细胞。在这里,我们首次证明,体外扩增的中枢神经系统前体在移植到大鼠大脑中后,会形成电活跃且功能连接的神经元。这些神经元表现出自发的和诱发的突触后事件,并对局灶性谷氨酸应用做出反应。将供体细胞移植到胎儿海马体中,并在出生后第一个月监测 CA1 区移植细胞中自发突触事件的幅度和频率。移植神经元上突触的形成表明移植中枢神经系统干细胞可用于研究体内突触发育,并对临床细胞替代疗法具有重要意义。
An understanding of developmental mechanisms and new cell therapies can be achieved by transplantation into the nervous system. Multipotential stem cells have been isolated from the foetal and adult central nervous system (CNS). Immortalized and primary precursor cells integrate into the developing brain generating both neurons and glia as defined by immunological and morphological criteria. Here we show for the first time that in vitro-expanded CNS precursors, upon transplantation into the brains of rats, form electrically active and functionally connected neurons. These neurons exhibit spontaneous and evoked postsynaptic events and respond to focal glutamate application. Donor cells were grafted into the foetal hippocampus, and the amplitude and frequency of spontaneous synaptic events were monitored in the grafted cells in area CA1 for the first month of postnatal life. The formation of synapses onto grafted neurons indicates that grafted CNS stem cells can be used to study synaptic development in vivo and has important implications for clinical cell replacement therapies.