Matsui Takeshi, Akamatsu Wado, Nakamura Masaya, Okano Hideyuki
Department of Physiology, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Department of Orthopedic Surgery, Keio University, School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Exp Neurol. 2014 Oct;260:12-8. doi: 10.1016/j.expneurol.2012.09.016. Epub 2012 Oct 1.
Neural stem cell (NSC) transplantation provides a new approach for the repair of damage to the central nervous system (CNS), including that resulting from cerebral infarction and spinal cord injury (SCI). In the past, there were no reputable means of converting non-neural somatic cells into neural cells. This status was overturned by the establishment of induced pluripotent stem (iPS) cells, which have pluripotency akin to that of embryonic stem (ES) cells and can differentiate into most cells of the three germ layers. If differentiated somatic cells could be reprogrammed into iPS cells, and if these iPS cells could be induced to differentiate once again, it would be theoretically possible to obtain a large number of neural cells. However, this is not yet feasible due to the limitations of existing stem cell technology. Induction of neural cells from iPS cells is currently hindered by two distinct problems: 1) the preparation of specific types of targeted neural cells requires extensive cell culture, and 2) tumors are likely to form due to the presence of residual undifferentiated cells following transplantation of the induced cells. By contrast, direct induction methods permit the generation of target cells from somatic cells without the transitional iPS cell stage. This review outlines the present-day status of research surrounding the direct induction of NSCs from somatic cells, as well as the perspectives for the future clinical application of this technique for cell replacement therapy following CNS injury.
神经干细胞(NSC)移植为修复中枢神经系统(CNS)损伤提供了一种新方法,这些损伤包括脑梗死和脊髓损伤(SCI)所导致的损伤。过去,没有可靠的方法将非神经体细胞转化为神经细胞。诱导多能干细胞(iPS细胞)的建立颠覆了这一状况,iPS细胞具有类似于胚胎干细胞(ES细胞)的多能性,能够分化为三个胚层的大多数细胞。如果分化的体细胞能够被重编程为iPS细胞,并且这些iPS细胞能够再次被诱导分化,那么从理论上来说就有可能获得大量神经细胞。然而,由于现有干细胞技术的局限性,这一点目前还不可行。目前,从iPS细胞诱导神经细胞受到两个明显问题的阻碍:1)制备特定类型的靶向神经细胞需要大量的细胞培养,2)诱导细胞移植后由于残留未分化细胞的存在可能会形成肿瘤。相比之下,直接诱导方法允许从体细胞产生靶细胞,而无需经过iPS细胞的过渡阶段。本综述概述了围绕从体细胞直接诱导神经干细胞的研究现状,以及该技术在中枢神经系统损伤后细胞替代治疗中的未来临床应用前景。