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Ischemia-Induced Multipotent Stem Cells Isolated from Stroke Patients Exhibit Higher Neurogenic Differentiation Potential than Bone Marrow-Derived Mesenchymal Stem Cells.
Stem Cells and Development ( IF 4 ) Pub Date : 2020-07-30 , DOI: 10.1089/scd.2020.0031
Saujanya Rajbhandari 1 , Mikiya Beppu 1 , Toshinori Takagi 1 , Akiko Nakano-Doi 2, 3 , Nami Nakagomi 4 , Tomohiro Matsuyama 3 , Takayuki Nakagomi 2, 3 , Shinichi Yoshimura 1, 2
Affiliation  

Perivascular areas of the brain harbor multipotent stem cells. We recently demonstrated that after a stroke, brain pericytes exhibit features of multipotent stem cells. Moreover, these ischemia-induced multipotent stem cells (iSCs) are present within ischemic areas of the brain of patients diagnosed with stroke. Although increasing evidence shows that iSCs have traits similar to those of mesenchymal stem cells (MSCs), the phenotypic similarities and differences between iSCs and MSCs remain unclear. In this study, we used iSCs extracted from stroke patients (h-iSCs) and compared their neurogenic potential with that of human MSCs (h-MSCs) in vitro. Microarray analysis, fluorescence-activated cell sorting, immunohistochemistry, and multielectrode array were performed to compare the characteristics of h-iSCs and h-MSCs. Although h-iSCs and h-MSCs had similar gene expression profiles, the percentage expressing the neural stem/progenitor cell marker nestin was significantly higher in h-iSCs than in h-MSCs. Consistent with these findings, h-iSCs, but not h-MSCs, differentiated into electrophysiologically functional neurons. In contrast, although both h-iSCs and h-MSCs were able to differentiate into several mesodermal lineages, including adipocytes, osteocytes, and chondrocytes, the potential of h-iSCs to differentiate into adipocytes and osteocytes was relatively low. These results suggest that compared with h-MSCs, h-iSCs predominantly exhibit neural rather than mesenchymal lineages. In addition, these results indicate that h-iSCs have the potential to repair the injured brain of patients with stroke by directly differentiating into neuronal lineages.

中文翻译:

从中风患者中分离的缺血诱导的多能干细胞表现出比骨髓源性间充质干细胞更高的神经源性分化潜能。

大脑的血管周围区域含有多能干细胞。我们最近证明,在中风后,脑周细胞表现出多能干细胞的特征。此外,这些缺血诱导的多能干细胞 (iSC) 存在于诊断为中风的患者大脑的缺血区域中。尽管越来越多的证据表明 iSCs 具有与间充质干细胞 (MSCs) 相似的特征,但 iSCs 和 MSCs 之间的表型异同仍不清楚。在这项研究中,我们使用了从中风患者 (h-iSCs) 中提取的 iSCs,并在体外将它们的神经源性潜力与人类 MSCs (h-MSCs) 的神经源性潜力进行了比较。进行微阵列分析、荧光激活细胞分选、免疫组织化学和多电极阵列以比较 h-iSCs 和 h-MSCs 的特征。尽管 h-iSCs 和 h-MSCs 具有相似的基因表达谱,但在 h-iSCs 中表达神经干/祖细胞标记巢蛋白的百分比明显高于 h-MSCs。与这些发现一致,h-iSCs,但不是 h-MSCs,分化为具有电生理功能的神经元。相比之下,尽管 h-iSCs 和 h-MSCs 都能够分化成几种中胚层谱系,包括脂肪细胞、骨细胞和软骨细胞,但 h-iSCs 分化为脂肪细胞和骨细胞的潜力相对较低。这些结果表明,与 h-MSCs 相比,h-iSCs 主要表现出神经谱系而不是间充质谱系。此外,这些结果表明 h-iSCs 具有通过直接分化为神经元谱系来修复中风患者受损大脑的潜力。
更新日期:2020-08-04
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