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周围神经源性干细胞球体诱导啮齿动物脊髓损伤后的功能恢复和修复。

Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents.

机构信息

Spine & Spinal Cord Institute, Department of Neurosurgery, College of Medicine, Yonsei University, Seoul 03722, Korea.

Paik Inje Memorial Institute for Clinical Research, Inje University College of Medicine, Busan 47392, Korea.

出版信息

Int J Mol Sci. 2021 Apr 16;22(8):4141. doi: 10.3390/ijms22084141.

Abstract

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.

摘要

干细胞治疗是脊髓损伤最有前途的候选治疗方法之一。这项治疗的研究结果令人乐观,但仍存在临床限制,包括存活率低、植入和分化能力差等问题。在这里,我们从成人外周神经中分离出具有与神经嵴干细胞相似特征的新型周围神经源性干细胞(PNSCs)。这些 PNSCs 表达神经嵴特异性标志物,并具有向施万细胞、神经胶质、神经元和中胚层细胞多谱系分化的潜力。此外,PNSCs 通过释放神经营养因子,如胶质细胞系衍生的神经营养因子、胰岛素样生长因子、神经生长因子和神经营养素-3,显示出治疗潜力。PNSCs 的能力也通过其发展成球体而增强,这些球体分泌的神经营养因子是非球体 PNSCs 的数倍,并表达多种细胞外基质。这些特征表明,这些 PNSC 球体具有克服其局限性的潜力。在动物脊髓损伤(SCI)模型中,这些 PNSC 球体诱导了功能恢复和神经元再生。这些 PNSC 球体还减少了 SCI 后髓鞘再生引起的神经病理性疼痛。这些 PNSC 球体可能为 SCI 患者提供一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0755/8072978/445c959a60e9/ijms-22-04141-g001.jpg

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