Mesenchymal Stem Cells for Ischemic Stroke: Changes in Effects After Ex Vivo Culturing
Mesenchymal Stem Cells for Ischemic Stroke: Changes in Effects After Ex Vivo Culturing
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DOI：
10.3727/096368908786991551
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Bang, Oh Young
中科院分区：
文献类型：
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作者：
Li, Wen Yu;Choi, Yun Jung;Bang, Oh Young
虽然离体培养扩增对于使用自体间充质干细胞（MSC）治疗中风患者是必要的，并且一些研究人员在他们的研究中利用了培养扩增的细胞，但培养扩增对神经发生和营养支持的影响尚不清楚。因此，我们评估了MSC的传代对其在大鼠中风模型中的作用的影响。在大鼠中风模型中进行离体培养的人MSC的IV应用，早期（第2代）或晚期（第6代）。行为学测试，免疫组织化学研究，并使用CAST网格系统进行定量分析，以评估神经发生的程度。我们还评估了对照组和MSC处理的大鼠脑提取物中营养因子的水平。与接受后期传代的人MSC的大鼠相比，在接受早期传代的人MSC的大鼠中，通过溴脱氧尿苷染色显示的行为恢复和神经发生更明显（在两种情况下p < 0.01）。双重染色显示，大多数内源性神经元祖细胞，但很少人MSC，表达神经元和胶质细胞表型。营养因子的组织水平，包括胶质细胞源性神经营养因子、神经生长因子、血管内皮生长因子和肝细胞生长因子，在早期传代MSC治疗的脑中高于对照组或晚期传代MSC治疗的脑（所有病例中p < 0.01）。我们的研究结果表明，缺血诱导的神经发生增强了静脉注射人骨髓间充质干细胞。早期传代的效果比晚期传代的人MSC更明显，这可能与营养支持能力的差异有关，取决于它们的传代。
Although ex vivo culture expansion is necessary to use autologous mesenchymal stem cells (MSCs) in treating stroke patients, and several researchers have utilized culture-expanded cells in their studies, the effects of culture expansion on neurogenesis and trophic support are unknown. Thus, we evaluated the impact of the passage of MSCs on their effects in a rat stroke model. The IV application of ex vivo-cultured human MSCs, earlier (passage 2) or later passage (passage 6), was performed in a rat stroke model. Behavioral tests, immunohistochemical studies, and quantitative analysis using the CAST-grid system were performed to evaluate the degree of neurogenesis. We also evaluated the levels of trophic factors in both control and MSC-treated rat brain extract. Compared to rats that received later-passage human MSCs, behavioral recovery and neurogenesis as revealed by bromodeoxyuridine staining were more pronounced in rats that received earlier-passage human MSCs (p < 0.01 in both cases). Double staining showed that most of the endogenous neuronal progenitor cells, but few human MSCs, expressed neuronal and glial phenotypes. Tissue levels of trophic factors, including glial cell line-derived neurotrophic factor, nerve growth factor, vascular endothelial growth factor, and hepatocyte growth factor, were higher in earlier-passage MSC-treated brains than in control or later-passage MSC-treated brains (p < 0.01 in all cases). Our results indicate that ischemia-induced neurogenesis was enhanced by the IV administration of human MSCs. The effects were more pronounced with earlier-passage than with later-passage human MSCs, which may be related to the differential capacity in trophic support, depending on their passage.