干细胞修复感觉神经损伤的研究进展

doi:10.3969/j.issn.1674-8115.2023.11.014

摘要/Abstract

摘要：

感觉神经属于周围神经系统的传入神经部分。它们的作用是接受机体内外刺激，传入中枢，形成感觉或反射。外伤、肿瘤侵犯、手术损伤等原因，均可导致感觉神经受损。感觉神经损伤可能会使患者的某些感觉器官功能减退或丧失，如视神经、听神经等重要感觉神经在受损后会给患者生活质量带来严重影响。目前临床上修复感觉神经的方法主要是自体神经移植，但其应用受到各种因素限制，神经功能的恢复效果也常常有限。干细胞具有多向分化潜能，可以分化成施万细胞，继而分泌神经营养因子促进轴突生长和髓鞘再生，施万细胞定向增殖形成宾格尔带，引导神经再生。干细胞也可以分化为神经元，构筑神经缺损的修复材料，是神经修复的理想选择。目前，以干细胞为基础，结合若干关键性的生物技术，例如利用生物聚合或人工合成的表面微图案化的神经导管实现神经缺损的桥接、利用微球实现细胞外基质蛋白和神经营养因子控制性释放等，形成的组织工程学技术正被广泛研究，并取得了一定的成果。该文就干细胞在几种主要的感觉神经如视神经、嗅神经、蜗神经及坐骨神经的感觉神经纤维等损伤修复中的研究进展进行综述，期望为干细胞的神经修复提供新的视角，拓宽干细胞在神经修复中的临床前研究，为后续的临床应用提供参考。

关键词: 感觉神经, 周围神经, 干细胞, 神经修复

Abstract:

Sensory nerves belong to the afferent nerve part of the peripheral nervous system. Their role is to accept the stimuli inside and outside the body and transmit them to the center nerve system to form sensations or reflexes. Sensory nerve damage can be caused by trauma, tumor invasion, surgical injury, etc. Sensory nerve injury may cause decline or loss of some sensory organs function in patients. Damage of important sensory nerves such as optic nerves and auditory nerves can bring profound troubles to patients' lives. So far, the main clinical method to repair sensory nerves is autologous nerve transplantation. However, its application is limited by various factors, and the recovery effect of nerve function is often limited. Stem cells have the potential of multi-directional differentiation, which can differentiate into Schwann cells, and then secrete neurotrophic factors to promote axonal growth and myelin regeneration. Schwann cells directionally proliferate and form Büngner zones which guide nerve regeneration. Stem cells can also differentiate into neurons and construct nerve defect repair materials, which is an ideal choice for nerve repair. At present, the tissue engineering technology based on stem cells, combined with several key biotechnology, such as the use of biopolymerized or artificial surface micro-patterning nerve conduit to bridge nerve defects, and the use of microspheres to achieve the controlled release of extracellular matrix proteins and neurotrophic factors, is being widely studied and has achieved certain research results. This article reviews the research progress of stem cells in the repair of several major sensory nerves, such as optic nerves, olfactory nerves, cochlear nerves and sensory nerve fibers of sciatic nerve, expecting to provide a new perspective for neural repair of stem cells, broaden the preclinical research in nerve repair, and provide reference for follow-up clinical application.

Key words: sensory nerve, peripheral nerve, stem cell, nerve repair

中图分类号:

Q819

陈惠东, 张云龙, 张志坚, 华清泉. 干细胞修复感觉神经损伤的研究进展[J]. 上海交通大学学报（医学版）, 2023, 43(11): 1450-1456.

CHEN Huidong, ZHANG Yunlong, ZHANG Zhijian, HUA Qingquan. Advances in stem cell therapy for sensory nerve injury[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2023, 43(11): 1450-1456.

图/表 1

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Model	Type	Route	Effect	Mechanism	Reference
Clamp injury in Lister hooded rats	UC-MSCs	Vitreous injection	The survival rate of RGC and the number of new axons and synapses were significantly increased	Factors that promote the survival or growth of target cells directly secreted or delivered through exocrine bodies	[6]
Crushing injury in SD rats	DPSCs/BMSCs	Vitreous injection	Both could promote the survival of RGC and the formation of neurite, with better effects on dental pulp stem cells	Neurotrophic effect of factors secreted by stem cells represented by NGF/BDNF/NT3	[7]
Unilateral olfactory nerve transection in SD rats	ADSCs	Caudal vein injection	The expression of OMP and the number of PCNA positive cells increased significantly	Secretion of neurotrophin and differentiation into olfactory neurons and olfactory epithelial cells affect the regeneration of olfactory epithelium	[18]
Olfactory epithelium injury induced by methimazole in mice	BMSCs/G-CSF	Caudal vein injection/hypodermic injection	There was a significant difference in survival rate of bone marrow cells implanted with G-CSF at different time	G-CSF mobilizes BMSCs from bone marrow to circulation and protects nerves by inhibiting neuronal apoptosis	[21]
Ten-mm defect of sciatic nerve in Wistar rats	ADSCs	Nerve conduit transplantation	Electrophysiological examination showed a significant recovery of sensory and motor function, and histological analysis showed that myelin reformation and axon growth were better than the control side	ADSCs secrete neurotrophin, which can promote the synthesis and correct localization of ECM in regenerated nerve tissue, and increase the chemotactic attraction of growth cone	[34]
Five-mm defect of left sciatic nerve in C57BL6 mice	iPSCs	Nerve conduit transplantation	The recovery of sensory and motor function in the iPSC group was significantly better than the control group, and histology suggested that myelin sheath and axon regeneration were significantly enhanced	iPSCs-derived neurospheres differentiate into Schwann cells, form myelin sheath or release nerve growth factor to promote axonal growth	[35]

Model	Type	Route	Effect	Mechanism	Reference
Clamp injury in Lister hooded rats	UC-MSCs	Vitreous injection	The survival rate of RGC and the number of new axons and synapses were significantly increased	Factors that promote the survival or growth of target cells directly secreted or delivered through exocrine bodies	[6]
Crushing injury in SD rats	DPSCs/BMSCs	Vitreous injection	Both could promote the survival of RGC and the formation of neurite, with better effects on dental pulp stem cells	Neurotrophic effect of factors secreted by stem cells represented by NGF/BDNF/NT3	[7]
Unilateral olfactory nerve transection in SD rats	ADSCs	Caudal vein injection	The expression of OMP and the number of PCNA positive cells increased significantly	Secretion of neurotrophin and differentiation into olfactory neurons and olfactory epithelial cells affect the regeneration of olfactory epithelium	[18]
Olfactory epithelium injury induced by methimazole in mice	BMSCs/G-CSF	Caudal vein injection/hypodermic injection	There was a significant difference in survival rate of bone marrow cells implanted with G-CSF at different time	G-CSF mobilizes BMSCs from bone marrow to circulation and protects nerves by inhibiting neuronal apoptosis	[21]
Ten-mm defect of sciatic nerve in Wistar rats	ADSCs	Nerve conduit transplantation	Electrophysiological examination showed a significant recovery of sensory and motor function, and histological analysis showed that myelin reformation and axon growth were better than the control side	ADSCs secrete neurotrophin, which can promote the synthesis and correct localization of ECM in regenerated nerve tissue, and increase the chemotactic attraction of growth cone	[34]
Five-mm defect of left sciatic nerve in C57BL6 mice	iPSCs	Nerve conduit transplantation	The recovery of sensory and motor function in the iPSC group was significantly better than the control group, and histology suggested that myelin sheath and axon regeneration were significantly enhanced	iPSCs-derived neurospheres differentiate into Schwann cells, form myelin sheath or release nerve growth factor to promote axonal growth	[35]

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