Department of Experimental Medical Science and Lund Stem Cell Center BMC, Lund University, 22141, Lund, Sweden.
Cell Mol Life Sci. 2019 Oct;76(20):3953-3967. doi: 10.1007/s00018-019-03193-3. Epub 2019 Jun 27.
The brain tissue has only a limited capacity for generating new neurons. Therefore, to treat neurological diseases, there is a need of other cell sources for brain repair. Different sources of cells have been subject of intense research over the years, including cells from primary tissue, stem cell-derived cells and reprogrammed cells. As an alternative, direct reprogramming of resident brain cells into neurons is a recent approach that could provide an attractive method for treating brain injuries or diseases as it uses the patient's own cells for generating novel neurons inside the brain. In vivo reprogramming is still in its early stages but holds great promise as an option for cell therapy. To date, both inhibitory and excitatory neurons have been obtained via in vivo reprogramming, but the precise phenotype or functionality of these cells has not been analysed in detail in most of the studies. Recent data shows that in vivo reprogrammed neurons are able to functionally mature and integrate into the existing brain circuitry, and compose interneuron phenotypes that seem to correlate to their endogenous counterparts. Interneurons are of particular importance as they are essential in physiological brain function and when disturbed lead to several neurological disorders. In this review, we describe a comprehensive overview of the existing studies involving brain repair, including in vivo reprogramming, with a focus on interneurons, along with an overview on current efforts to generate interneurons for cell therapy for a number of neurological diseases.
脑组织生成新神经元的能力有限。因此,为了治疗神经疾病,需要寻找其他的细胞来源来修复大脑。多年来,人们对多种细胞来源进行了深入研究,包括原代组织细胞、干细胞衍生细胞和重编程细胞。作为一种替代方法,直接将脑内固有细胞重编程为神经元是一种新方法,它利用患者自身的细胞在大脑内产生新的神经元,为治疗脑损伤或疾病提供了一种有吸引力的方法。体内重编程仍处于早期阶段,但作为细胞治疗的一种选择具有很大的潜力。迄今为止,通过体内重编程已经获得了抑制性神经元和兴奋性神经元,但在大多数研究中,这些细胞的精确表型或功能尚未详细分析。最近的数据表明,体内重编程的神经元能够功能性成熟并整合到现有的大脑回路中,并组成似乎与内源性神经元相对应的中间神经元表型。中间神经元尤为重要,因为它们是生理大脑功能所必需的,而当它们受到干扰时会导致多种神经疾病。在这篇综述中,我们全面描述了现有的涉及脑修复的研究,包括体内重编程,重点是中间神经元,并概述了目前为治疗多种神经疾病而生成中间神经元用于细胞治疗的努力。