Department of Biotechnology and Biosciences, University of Milan-Bicocca, Italy.
Stem Cells Transl Med. 2012 Apr;1(4):298-308. doi: 10.5966/sctm.2011-0045. Epub 2012 Apr 10.
The recent discovery of neural stem cells (NSCs) in the adult mammalian brain has fostered a plethora of translational and preclinical studies to investigate future therapeutic approaches for the cure of neurodegenerative diseases. These studies are finally at the clinical stage, and some of them are already under way. The definition of a bona fide stem cell has long been the object of much debate focused on the establishment of standard and univocal criteria to distinguish between stem and progenitor cells. It is commonly accepted that NSCs have to fulfill two basic requirements, the capacity for long-term self-renewal and the potential for differentiation, which account for their physiological role, namely central nervous system tissue homeostasis. Strategies such as immortalization or reprogramming of somatic cells to the embryonic-like stage of pluripotency indicate the relevance of extensive self-renewal ability of NSCs either in vitro or in vivo. Moreover, the discovery of stem-like tumor cells in brain tumors, such as gliomas, accompanied by the isolation of these cells through the same paradigm used for related healthy cells, has provided further evidence of the key role that self-renewal plays in the development and progression of neurodegenerative diseases and cancer. In this review we provide an overview of the current understanding of the self-renewal capacity of nontransformed human NSCs, with or without immortalization or reprogramming, and of stem-like tumor cells, referring to both research and therapeutic studies.
最近在成年哺乳动物大脑中发现了神经干细胞 (NSC),这促进了大量转化和临床前研究,以探索治疗神经退行性疾病的未来治疗方法。这些研究终于进入了临床阶段,其中一些已经在进行中。真正的干细胞的定义长期以来一直是许多争论的焦点,这些争论集中在建立标准和明确的标准来区分干细胞和祖细胞。人们普遍认为,NSC 必须满足两个基本要求,即长期自我更新的能力和分化的潜力,这解释了它们的生理作用,即中枢神经系统组织的动态平衡。通过将体细胞永生化或重编程为多能性的胚胎样状态等策略表明,NSC 在体外或体内都具有广泛的自我更新能力。此外,在脑肿瘤(如神经胶质瘤)中发现了类似于干细胞的肿瘤细胞,并且通过与相关健康细胞相同的范例对这些细胞进行了分离,这进一步证明了自我更新在神经退行性疾病和癌症的发展和进展中起着关键作用。在这篇综述中,我们概述了目前对未转化的人类 NSC 的自我更新能力的理解,无论是否永生化或重编程,以及类似干细胞的肿瘤细胞,同时参考了研究和治疗研究。