ABSTRACT

Nervous system diseases, especially degenerative diseases of the central nervous system (CNS), seriously endanger human health, and the injured adult neurons are difficult to self-renew. Therefore, cell replacement therapy with good application prospects has become a hot spot in biomedical research. Human embryonic stem cells (hESCs) are promising sources of cells with unlimited proliferation ability and multiple differentiation potential. The purpose of this study was to use these characteristics of hESCs to obtain a large number of differentiated and stable neural stem cells (NSCs) and provide potential tissue engineering materials for the treatment of neurological diseases. Cultured on low adhesion plate for 4 days in vitro, the hESCs can differentiate into suspended embryoid bodies (EBs). After further culture of EBs for 4 days, high-purity Nestin-positive NSCs with typical rosette structure can be induced, and these cells can further differentiate into a variety of mature nerve cells. Meanwhile, hESCs could form in vivo typical teratomas that contained rosette structures. Our results indicated that hESCs had the ability to differentiate into rosette NSCs both in vitro and in vivo, and the bioactive rosettes are of great significance to understanding the mechanism of neural development and studying the treatment of neurodegenerative diseases.

摘要

神经系统疾病，特别是中枢神经系统退行性疾病严重危害人类健康，受伤的成年神经元很难自我更新。因此，具有良好应用前景的细胞替代疗法已成为生物医学研究的热点。人类胚胎干细胞（hESCs）是具有无限增殖能力和多重分化潜能的有前途的细胞来源。这项研究的目的是利用hESC的这些特征来获得大量分化和稳定的神经干细胞（NSC），并为治疗神经系统疾病提供潜在的组织工程材料。在低粘附力平板上体外培养4天，hESC可以分化为悬浮的胚状体（EB）。将EB进一步培养4天后，可以诱导出具有典型玫瑰花结结构的高纯度Nestin阳性NSC，这些细胞可以进一步分化为各种成熟的神经细胞。同时，hESCs可以在体内形成包含玫瑰花结结构的典型畸胎瘤。我们的结果表明，hESCs能够在体外和体内分化为玫瑰花样NSC ，而具有生物活性的玫瑰花样对于理解神经发育的机制和研究神经退行性疾病的治疗具有重要意义。