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成人间充质干细胞支持顺铂处理后的背根神经节存活。

Adult mesenchymal stem cells support cisplatin-treated dorsal root ganglion survival.

作者信息

Scuteri Arianna, Donzelli Elisabetta, Ravasi Maddalena, Tredici Giovanni

机构信息

Dipartimento di Neuroscienze e Tecnologie Biomediche, Università degli Studi di Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy.

出版信息

Neurosci Lett. 2008 Nov 7;445(1):68-72. doi: 10.1016/j.neulet.2008.08.056. Epub 2008 Aug 27.

Abstract

Mesenchymal stem cells (MSCs) have been found to be useful in the management of different models of neurological diseases. In the present study, we tested the possible protective effect of MSCs on sensory dorsal root ganglia (DRG) explants exposed to the toxic effect of CDDP, a widely used anticancer drug. DRG explants cultured on a collagen layer and exposed to NGF for 2h (differentiating neurons) or for 5 days (fully differentiated neurons) were treated with CDDP and subsequently co-cultured with MSCs. MSCs were able to support the survival of both differentiating and fully differentiated DRG neurons up to 2 months after the drug treatment, reducing the CDDP-induced death of DRG neurons. MSCs were, however, unable to restore the correct length of DRG neurites compromised by CDDP treatment. The positive effect on neuronal survival was exerted through the contact between DRG and MSCs, and not mediated by neurotrophic factors released by the MSCs. Our observations could represent a starting point for designing a neuroprotective strategy to limit CDDP induced neuropathy without interfering with its anticancer properties.

摘要

间充质干细胞(MSCs)已被发现可用于治疗不同模型的神经疾病。在本研究中,我们测试了MSCs对暴露于广泛使用的抗癌药物顺铂(CDDP)毒性作用下的感觉背根神经节(DRG)外植体的可能保护作用。在胶原层上培养并暴露于神经生长因子(NGF)2小时(分化中的神经元)或5天(完全分化的神经元)的DRG外植体先用CDDP处理,随后与MSCs共培养。在药物处理后长达2个月的时间里,MSCs能够支持分化中和完全分化的DRG神经元的存活,减少CDDP诱导的DRG神经元死亡。然而,MSCs无法恢复因CDDP处理而受损的DRG神经突的正确长度。对神经元存活的积极作用是通过DRG与MSCs之间的接触发挥的,而不是由MSCs释放的神经营养因子介导的。我们的观察结果可能代表了设计一种神经保护策略的起点,该策略可以在不干扰其抗癌特性的情况下限制CDDP诱导的神经病变。

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