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从嗅活检中分离出的人骨髓基质细胞而非骨细胞在体外增强中枢神经系统髓鞘形成。

Human mesenchymal stem cells isolated from olfactory biopsies but not bone enhance CNS myelination in vitro.

机构信息

Institute of Infection, Immunity and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow, United Kingdom.

出版信息

Glia. 2013 Mar;61(3):368-82. doi: 10.1002/glia.22440. Epub 2012 Dec 22.

Abstract

Spinal cord injury (SCI) is a devastating condition with limited capacity for repair. Cell transplantation is a potential strategy to promote SCI repair with cells from the olfactory system being promising candidates. Although transplants of human olfactory mucosa (OM) are already ongoing in clinical trials, the repair potential of this tissue remains unclear. Previously, we identified mesenchymal-like stem cells that reside in the lamina propria (LP-MSCs) of rat and human OM. Little is known about these cells or their interactions with glia such as olfactory ensheathing cells (OECs), which would be co-transplanted with MSCs from the OM, or endogenous CNS glia such as oligodendrocytes. We have characterized, purified, and assessed the repair potential of human LP-MSCs by investigating their effect on glial cell biology with specific emphasis on CNS myelination in vitro. Purified LP-MSCs expressed typical bone marrow MSC (BM-MSC) markers, formed spheres, were clonogenic and differentiated into bone and fat. LP-MSC conditioned medium (CM) promoted oligodendrocyte precursor cell (OPC) and OEC proliferation and induced a highly branched morphology. LP-MSC-CM treatment caused OEC process extension. Both LP and BM-MSCs promoted OPC proliferation and differentiation, but only myelinating cultures treated with CM from LP and not BM-MSCs had a significant increase in myelination. Comparison with fibroblasts and contaminating OM fibroblast like-cells showed the promyelination effect was LP-MSC specific. Thus LP-MSCs harvested from human OM biopsies may be an important candidate for cell transplantation by contributing to the repair of SCI.

摘要

脊髓损伤(SCI)是一种具有有限修复能力的破坏性疾病。细胞移植是一种促进 SCI 修复的潜在策略,其中嗅神经系统的细胞是有前途的候选者。尽管来自人类嗅黏膜(OM)的移植已经在临床试验中进行,但这种组织的修复潜力仍不清楚。以前,我们鉴定了位于大鼠和人 OM 固有层(LP-MSCs)中的间充质样干细胞。对于这些细胞或它们与嗅鞘细胞(OEC)等胶质细胞的相互作用知之甚少,OEC 将与 OM 中的 MSC 一起共移植,或与内源性中枢神经系统胶质细胞(如少突胶质细胞)相互作用。我们已经通过研究其对胶质细胞生物学的影响,特别是在体外 CNS 髓鞘形成方面,对人 LP-MSCs 的特征、纯化和修复潜力进行了表征、纯化和评估。纯化的 LP-MSCs 表达典型的骨髓 MSC(BM-MSC)标志物,形成球体,具有克隆形成能力,并分化为骨和脂肪。LP-MSC 条件培养基(CM)促进少突胶质细胞前体细胞(OPC)和 OEC 的增殖,并诱导出高度分支的形态。LP-MSC-CM 处理可导致 OEC 过程延伸。LP 和 BM-MSCs 均促进 OPC 的增殖和分化,但只有用来自 LP 而不是 BM-MSCs 的 CM 处理的髓鞘形成培养物才有明显的髓鞘形成增加。与成纤维细胞和污染的 OM 成纤维细胞样细胞的比较表明,促髓鞘形成作用是 LP-MSC 特异性的。因此,从人 OM 活检中收获的 LP-MSCs 可能是细胞移植的重要候选物,可有助于 SCI 的修复。

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