Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain
Embryonic stem cell-derived neuronally committed precursor cells with reduced teratoma formation after transplantation into the lesioned adult mouse brain
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DOI：
10.1634/stemcells.2005-0413
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发表时间：
2006-06-01
期刊：
影响因子：
5.2
通讯作者：
Schachner, Melitta
中科院分区：
文献类型：
--
作者：
Dihne, Marcel;Bernreuther, Christian;Schachner, Melitta
胚胎干细胞在神经退行性疾病中的治疗潜力已被广泛认识，并正在开发方法来优化培养条件，以丰富感兴趣的细胞，并提高移植后的移植物稳定性和安全性。虽然胚胎干细胞来源的神经后代的异种移植模式中很少发生畸胎瘤的形成，但接受小鼠胚胎干细胞来源的神经前体细胞移植的小鼠中，超过70%的小鼠会发生畸胎瘤，因此对异基因和同基因移植模式构成了一个主要的安全问题。在这里，我们介绍了一种新的分化方案，该方案基于基质黏附的ES细胞衍生的神经聚集体(SENA)的产生，该聚集体主要由神经元承诺的前体细胞组成。纯化的Senas被分化成未成熟的有丝分裂后神经元，在同种异体移植到急剧退化的纹状体后四个月内没有形成肿瘤，并表现出强劲的存活。
The therapeutic potential of embryonic stem (ES) cells in neurodegenerative disorders has been widely recognized, and methods are being developed to optimize culture conditions for enriching the cells of interest and to improve graft stability and safety after transplantation. Whereas teratoma formation rarely occurs in xenogeneic transplantation paradigms of ES cell-derived neural progeny, more than 70% of mice that received murine ES cell-derived neural precursor cells develop teratomas, thus posing a major safety problem for allogeneic and syngeneic transplantation paradigms. Here we introduce a new differentiation protocol based on the generation of substrate-adherent ES cell-derived neural aggregates (SENAs) that consist predominantly of neuronally committed precursor cells. Purified SENAs that were differentiated into immature but postmitotic neurons did not form tumors up to four months after syngeneic transplantation into the acutely degenerated striatum and showed robust survival.