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通过施万细胞和转分化骨髓基质细胞移植实现中枢和外周神经再生

Central and peripheral nerve regeneration by transplantation of Schwann cells and transdifferentiated bone marrow stromal cells.

作者信息

Dezawa Mari

机构信息

Department of Anatomy, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.

出版信息

Anat Sci Int. 2002 Mar;77(1):12-25. doi: 10.1046/j.0022-7722.2002.00012.x.

Abstract

In contrast to the peripheral nervous system (PNS), little structural and functional regeneration of the central nervous system (CNS) occurs spontaneously following injury in adult mammals. The inability of the CNS to regenerate is mainly attributed to its own inhibitorial environment such as glial scar formation and the myelin sheath of oligodendrocytes. Therefore, one of the strategies to promote axonal regeneration of the CNS is to experimentally modify the environment to be similar to that of the PNS. Schwann cells are the myelinating glial cells in the PNS, and are known to play a key role in Wallerian degeneration and subsequent regeneration. Central nervous system regeneration can be elicited by Schwann cell transplantation, which provides a suitable environment for regeneration. The underlying cellular mechanism of regeneration is based upon the cooperative interactions between axons and Schwann cells involving the production of neurotrophic factors and other related molecules. Furthermore, tight and gap junctional contact between the axon and Schwann cell also mediates the molecular interaction and linking. In this review, the role of the Schwann cell during the regeneration of the sciatic (representing the PNS) and optic (representing the CNS) nerves is explained. In addition, the possibility of optic nerve reconstruction by an artificial graft of Schwann cells is also described. Finally, the application of cells not of neuronal lineage, such as bone marrow stromal cells (MSCs), in nerve regeneration is proposed. Marrow stromal cells are known as multipotential stem cells that, under specific conditions, differentiate into several kinds of cells. The strategy to transdifferentiate MSCs into the cells with a Schwann cell phenotype and the induction of sciatic and optic nerve regeneration are described.

摘要

与周围神经系统(PNS)不同,成年哺乳动物中枢神经系统(CNS)损伤后很少会自发出现结构和功能的再生。中枢神经系统无法再生主要归因于其自身的抑制性环境,如胶质瘢痕形成和少突胶质细胞的髓鞘。因此,促进中枢神经系统轴突再生的策略之一是通过实验将环境改变为类似于周围神经系统的环境。雪旺细胞是周围神经系统中的髓鞘形成胶质细胞,已知在沃勒变性及随后的再生过程中起关键作用。雪旺细胞移植可引发中枢神经系统再生,为再生提供合适的环境。再生的潜在细胞机制基于轴突与雪旺细胞之间的协同相互作用,涉及神经营养因子和其他相关分子的产生。此外,轴突与雪旺细胞之间紧密和间隙连接接触也介导分子相互作用和连接。在这篇综述中,解释了雪旺细胞在坐骨神经(代表周围神经系统)和视神经(代表中枢神经系统)再生过程中的作用。此外,还描述了通过雪旺细胞人工移植重建视神经的可能性。最后,提出了非神经元谱系细胞,如骨髓基质细胞(MSCs)在神经再生中的应用。骨髓基质细胞是已知的多能干细胞,在特定条件下可分化为多种细胞。描述了将骨髓基质细胞转分化为具有雪旺细胞表型的细胞以及诱导坐骨神经和视神经再生的策略。

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