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中华移植杂志(电子版) ›› 2025, Vol. 19 ›› Issue (05) : 368 -374. doi: 10.3877/cma.j.issn.1674-3903.2025.05.013

综述

神经干细胞移植治疗脊髓损伤的机制研究进展
赵璨, 张蕾()   
  1. 226001 南通,南通大学医学院
  • 收稿日期:2025-02-13 出版日期:2025-10-25
  • 通信作者: 张蕾

Research progress on the mechanisms of neural stem cells transplantation in the treatment of spinal cord injury

Can Zhao, Lei Zhang()   

  1. Medical School of Nantong University, Nantong 226001, China
  • Received:2025-02-13 Published:2025-10-25
  • Corresponding author: Lei Zhang
引用本文:

赵璨, 张蕾. 神经干细胞移植治疗脊髓损伤的机制研究进展[J/OL]. 中华移植杂志(电子版), 2025, 19(05): 368-374.

Can Zhao, Lei Zhang. Research progress on the mechanisms of neural stem cells transplantation in the treatment of spinal cord injury[J/OL]. Chinese Journal of Transplantation(Electronic Edition), 2025, 19(05): 368-374.

脊髓损伤是一种严重的中枢神经系统创伤性病变,患者表现为损伤平面以下感觉、运动及自主神经功能障碍。神经干细胞(NSCs)具有强大的自我更新能力、多向分化潜能以及独特的微环境调节功能。本文重点围绕NSCs移植治疗脊髓损伤的作用机制进行综述。研究表明,NSCs不仅可分化成神经细胞,更可通过复杂的细胞间相互作用和微环境调控机制,在神经保护、轴突再生和神经环路重建中发挥重要作用。然而,NSCs移植治疗脊髓损伤仍面临移植细胞存活率低、定向分化效率不足和胶质瘢痕阻碍等挑战。未来可结合基因技术并运用生物材料,提升细胞存活能力以及改善受损微环境,从而推动NSCs移植治疗脊髓损伤的研究从基础走向临床,为脊髓损伤患者带来新的希望。

Spinal cord injury (SCI) is a severe traumatic lesion of the central nervous system, in which patients present with sensory, motor and autonomic nerve dysfunction below the level of the injury. Neural stem cells (NSCs) possess robust self-renewal capacity, multi-directional differentiation potential, and unique microenvironment regulatory functions. This article focuses on elaborating the mechanisms of NSCs transplantation for the treatment of SCI. Studies have shown that NSCs can not only differentiate into nerval cells, but also play a crucial role in neuroprotection, axonal regeneration, and neural circuit reconstruction through complex intercellular interactions and microenvironment regulatory mechanisms. However, NSCs transplantation for the treatment of SCI still faces challenges such as low survival rate of transplanted cells, insufficient efficiency of directed differentiation, and obstruction by glial scarring. Future studies may integrate genetic technologies and utilize biomaterials to enhance cell survival capacity and improve the damaged microenvironment, thereby advancing the researches on NSCs transplantation for SCI from basic studies to clinical application and bringing new hope to patients with SCI.

图1 神经干细胞移植治疗脊髓损伤的机制示意图
1
Hamid R, Averbeck MA, Chiang H, et al. Epidemiology and pathophysiology of neurogenic bladder after spinal cord injury[J]. World J Urol, 2018, 36(10):1517-1527.
2
Alizadeh A, Dyck SM, Karimi-Abdolrezaee S. Traumatic spinal cord injury: an overview of pathophysiology, models and acute injury mechanisms[J]. Front Neurol, 2019, 10:282.
3
Müller-Jensen L, Ploner CJ, Kroneberg D, et al. Clinical presentation and causes of non-traumatic spinal cord injury: an observational study in emergency patients[J]. Front Neurol, 2021, 12:701927.
4
Shi Z, Yuan S, Shi L, et al. Programmed cell death in spinal cord injury pathogenesis and therapy[J]. Cell Prolif, 2021, 54(3):e12992.
5
Fehlings MG, Tetreault LA, Wilson JR, et al. A clinical practice guideline for the management of acute spinal cord injury: introduction, rationale, and scope[J]. Global Spine J, 2017, 7 (3 Suppl):84S-94S.
6
Katoh H, Yokota K, Fehlings MG. Regeneration of spinal cord connectivity through stem cell transplantation and biomaterial scaffolds[J]. Front Cell Neurosci, 2019, 13:248.
7
Yang Y, Pang M, Chen YY, et al. Human umbilical cord mesenchymal stem cells to treat spinal cord injury in the early chronic phase: study protocol for a prospective, multicenter, randomized, placebo-controlled, single-blinded clinical trial[J]. Neural Regen Res, 2020, 15(8):1532-1538.
8
Gao L, Peng Y, Xu W, et al. Progress in stem cell therapy for spinal cord injury[J]. Stem Cells Int, 2020:2853650.
9
Okano H. Neural stem cells and strategies for the regeneration of the central nervous system[J]. Proc Jpn Acad Ser B Phys Biol Sci, 2010, 86(4): 438-450.
10
Salewski RP, Mitchell RA, Shen C, et al. Transplantation of neural stem cells clonally derived from embryonic stem cells promotes recovery after murine spinal cord injury[J]. Stem Cells Dev, 2015, 24(1):36-50.
11
Kong D, Feng B, Amponsah AE, et al. hiPSC-derived NSCs effectively promote the functional recovery of acute spinal cord injury in mice[J]. Stem Cell Res Ther, 2021, 12(1):172.
12
Jeong J, Choi Y, Kim N, et al. Effects of human neural stem cells overexpressing neuroligin and neurexin in a spinal cord injury model[J]. Int J Mol Sci, 2024, 25(16):8744.
13
Curtis E, Martin JR, Gabel B, et al. A first-in-human, phase I study of neural stem cell transplantation for chronic spinal cord injury[J]. Cell Stem Cell, 2018, 22(6):941-950.e6.
14
Bond AM, Ming GL, Song H. Adult mammalian neural stem cells and neurogenesis: five decades later[J]. Cell Stem Cell, 201517(4):385-395.
15
Sugai K, Sumida M, Shofuda T, et al. First-in-human clinical trial of transplantation of iPSC-derived NS/PCs in subacute complete spinal cord injury: study protocol[J]. Regen Ther, 2021, 18:321-333.
16
Jung JW, Jeong JH, Ko MJ, et al. Induced neural stem cell transplantation in spinal cord injury: present status and next steps[J]. Korean J Neurotrauma, 2024, 20(4):234-245.
17
Gu W, Zhang X, Yuan X, et al. Improving neuronal recovery in spinal cord injury with NEP1-40-modified neural stem cells through RhoA/ROCK signaling pathway modulation[J]. Biochim Biophys Acta Mol Basis Dis, 2025, 1871(7):167929.
18
Lv Y, Ji L, Dai H, et al. Identification of key regulatory genes involved in myelination after spinal cord injury by GSEA analysis[J]. Exp Neurol, 2024, 382:114966.
19
Hosseini SM, Nemati S, Karimi-Abdolrezaee S. Astrocytes originated from neural stem cells drive the regenerative remodeling of pathologic CSPGs in spinal cord injury[J]. Stem Cell Reports, 2024, 19(10):1451-1473.
20
Fan L, Liu C, Chen X, et al. Directing induced pluripotent stem cell derived neural stem cell fate with a three-dimensional biomimetic hydrogel for spinal cord injury repair[J]. ACS Appl Mater Interfaces, 2018, 10(21):17742-17755.
21
Liu JA, Tam KW, Chen YL, et al. Transplanting human neural stem cells with ≈50% reduction of SOX9 gene dosage promotes tissue repair and functional recovery from severe spinal cord injury[J]. Adv Sci (Weinh), 202310(20):e2205804.
22
Lutfi Ismaeel G, Makki AlHassani OJ, S Alazragi R, et al. Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state-of-the-art[J]. Biotechnol Prog, 2023, 39(5):e3363.
23
McGinley LM, Sims E, Lunn JS, et al. Human cortical neural stem cells expressing insulin-like growth factor-I: a novel cellular therapy for alzheimer′s disease[J]. Stem Cells Transl Med, 2016, 5(3):379-391.
24
Chang DJ, Cho HY, Hwang S, et al. Therapeutic effect of BDNF-overexpressing human neural stem cells (F3.BDNF) in a contusion model of spinal cord injury in rats[J]. Int J Mol Sci, 2021, 22(13):6970.
25
Wang L, Gu S, Gan J, et al. Neural stem cells overexpressing nerve growth factor improve functional recovery in rats following spinal cord injury via modulating microenvironment and enhancing endogenous neurogenesis[J]. Front Cell Neurosci, 2021, 15:773375.
26
Li G, Zhang B, Sun JH, et al. An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury[J]. Bioact Mater, 2021, 6(11):3766-3781.
27
Liu D, Shen H, Zhang K, et al. Functional hydrogel co-remolding migration and differentiation microenvironment for severe spinal cord injury repair[J]. Adv Healthc Mater, 2024, 13(3):e2301662.
28
Hellenbrand DJ, Quinn CM, Piper ZJ, et al. Inflammation after spinal cord injury: a review of the critical timeline of signaling cues and cellular infiltration[J]. J Neuroinflammation, 2021, 18(1):284.
29
Freyermuth-Trujillo X, Segura-Uribe JJ, Salgado-Ceballos H, et al. Inflammation: a target for treatment in spinal cord injury[J]. Cells, 2022, 11(17):2692.
30
Singh N, Pathak Z, Kumar H. Rab27a-mediated extracellular vesicle release drives astrocytic CSPG secretion and glial scarring in spinal cord injury[J]. Biomater Adv, 2025, 176:214357.
31
Cheng Z, Zhu W, Cao K, et al. Anti-inflammatory mechanism of neural stem cell transplantation in spinal cord injury[J]. Int J Mol Sci, 2016, 17(9):1380.
32
Semita IN, Utomo DN, Suroto H. Mechanism of spinal cord injury regeneration and the effect of human neural stem cells-secretome treatment in rat model[J]. World J Orthop, 2023, 14(2):64-82.
33
Kumamaru H, Kadoya K, Adler AF, et al. Generation and post-injury integration of human spinal cord neural stem cells[J]. Nat Methods, 2018, 15(9):723-731.
34
Li Y, Tran A, Graham L, et al. BDNF guides neural stem cell-derived axons to ventral interneurons and motor neurons after spinal cord injury[J]. Exp Neurol, 2023, 359:114259.
35
Hwang K, Jung K, Kim IS, et al. Glial cell line-derived neurotrophic factor-overexpressing human neural stem/progenitor cells enhance therapeutic efficiency in rat with traumatic spinal cord injury[J]. Exp Neurobiol, 2019, 28(6):679-696.
36
Ceto S, Sekiguchi KJ, Takashima Y, et al. Neural stem cell grafts form extensive synaptic networks that integrate with host circuits after spinal cord injury[J]. Cell Stem Cell, 2020, 27(3):430-440.e5.
37
Li Z, Guo GH, Wang GS, et al. Influence of neural stem cell transplantation on angiogenesis in rats with spinalcord injury[J]. Genet Mol Res, 2014, 13(3):6083-6092.
38
Zhong D, Cao Y, Li CJ, et al. Neural stem cell-derived exosomes facilitate spinal cord functional recovery after injury by promoting angiogenesis[J]. Exp Biol Med (Maywood), 2020, 245(1):54-65.
39
Miao X, Lin J, Li A, et al. AAV- mediated VEGFA overexpression promotes angiogenesis and recovery of locomotor function following spinal cord injury via PI3K/Akt signaling[J]. Exp Neurol, 2024, 375:114739.
40
Wu W, Jia S, Xu H, et al. Supramolecular hydrogel microspheres of platelet-derived growth factor mimetic peptide promote recovery from spinal cord injury[J]. ACS Nano, 2023, 17(4):3818-3837.
41
Rong Y, Liu W, Wang J, et al. Neural stem cell-derived small extracellular vesicles attenuate apoptosis and neuroinflammation after traumatic spinal cord injury by activating autophagy[J]. Cell Death Dis, 2019, 10(5):340.
42
Chen NN, Wei F, Wang L, et al. Tumor necrosis factor alpha induces neural stem cell apoptosis through activating p38 MAPK pathway[J]. Neurochem Res, 2016, 41(11):3052-3062.
43
Yue T, Li X, Chen X, et al. Hemoglobin derived from subarachnoid hemorrhage-induced pyroptosis of neural stem cells via ROS/ NLRP3/GSDMD pathway[J]. Oxid Med Cell Longev, 2023:4383332.
44
Qi Z, Pan S, Yang X, et al. Injectable hydrogel loaded with CDs and FTY720 combined with neural stem cells for the treatment of spinal cord injury[J]. Int J Nanomedicine, 2024, 19: 4081-4101.
45
Garone C, De Giorgio F, Carli S. Mitochondrial metabolism in neural stem cells and implications for neurodevelopmental and neurodegenerative diseases[J]. J Transl Med, 2024, 22(1):238.
46
Zheng Y, Huang Z, Xu J, et al. MiR- 124 and small molecules synergistically regulate the generation of neuronal cells from rat cortical reactive astrocytes[J]. Mol Neurobiol, 2021, 58(5): 2447-2464.
47
Qu W, Wu X, Wu W, et al. Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury[J]. Neural Regen Res, 2025, 20(5):1467-1482.
48
Nabeel Mustafa A, Salih Mahdi M, Ballal S, et al. Netrin-1: key insights in neural development and disorders[J]. Tissue Cell, 2025, 93:102678.
49
Tang L, Song Z, Wang J, et al. Regulatory role of neuronal guidance proteins in spinal cord injury[J].Neural Regen Res, 2025. [Online ahead of print]
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