人牙干细胞在修复大鼠脊髓完全横断损伤中的潜力

Potential of human dental stem cells in repairing the complete transection of rat spinal cord.

作者信息

Yang Chao, Li Xinghan, Sun Liang, Guo Weihua, Tian Weidong

机构信息

National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, People's Republic of China.

出版信息

J Neural Eng. 2017 Apr;14(2):026005. doi: 10.1088/1741-2552/aa596b. Epub 2017 Jan 13.

Abstract

OBJECTIVE

The adult spinal cord of mammals contains a certain amount of neural precursor cells, but these endogenous cells have a limited capacity for replacement of lost cells after spinal cord injury. The exogenous stem cells transplantation has become a therapeutic strategy for spinal cord repairing because of their immunomodulatory and differentiation capacity. In addition, dental stem cells originating from the cranial neural crest might be candidate cell sources for neural engineering.

APPROACH

Human dental follicle stem cells (DFSCs), stem cells from apical papilla (SCAPs) and dental pulp stem cells (DPSCs) were isolated and identified in vitro, then green GFP-labeled stem cells with pellets were transplanted into completely transected spinal cord. The functional recovery of rats and multiple neuro-regenerative mechanisms were explored.

MAIN RESULTS

The dental stem cells, especially DFSCs, demonstrated the potential in repairing the completely transected spinal cord and promote functional recovery after injury. The major involved mechanisms were speculated below: First, dental stem cells inhibited the expression of interleukin-1β to reduce the inflammatory response; second, they inhibited the expression of ras homolog gene family member A (RhoA) to promote neurite regeneration; third, they inhibited the sulfonylurea receptor1 (SUR-1) expression to reduce progressive hemorrhagic necrosis; lastly, parts of the transplanted cells survived and differentiated into mature neurons and oligodendrocytes but not astrocyte, which is beneficial for promoting axons growth.

SIGNIFICANCE

Dental stem cells presented remarkable tissue regenerative capability after spinal cord injury through immunomodulatory, differentiation and protection capacity.

摘要

目的

哺乳动物的成年脊髓含有一定数量的神经前体细胞,但这些内源性细胞在脊髓损伤后替代丢失细胞的能力有限。外源性干细胞移植因其免疫调节和分化能力已成为脊髓修复的一种治疗策略。此外,源自颅神经嵴的牙干细胞可能是神经工程的候选细胞来源。

方法

体外分离并鉴定人牙囊干细胞(DFSCs)、根尖乳头干细胞(SCAPs)和牙髓干细胞(DPSCs),然后将绿色GFP标记的干细胞与微球一起移植到完全横断的脊髓中。探讨大鼠的功能恢复和多种神经再生机制。

主要结果

牙干细胞,尤其是DFSCs,显示出修复完全横断脊髓并促进损伤后功能恢复的潜力。推测主要涉及的机制如下:第一,牙干细胞抑制白细胞介素-1β的表达以减轻炎症反应;第二,它们抑制Ras同源基因家族成员A(RhoA)的表达以促进神经突再生;第三,它们抑制磺脲类受体1(SUR-1)的表达以减少进行性出血性坏死;最后,部分移植细胞存活并分化为成熟神经元和少突胶质细胞,而非星形胶质细胞,这有利于促进轴突生长。

意义

牙干细胞在脊髓损伤后通过免疫调节、分化和保护能力表现出显著的组织再生能力。

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