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首页> 外文期刊>BMC Neuroscience >Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression
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Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression

机译：人骨髓间充质基质细胞的神经分化潜能：误导标记基因表达

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Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be inappropriate for transplantation strategies.
机译：背景技术与多能胚胎干细胞相反，成年干细胞被认为是多能的，它们的分化能力受到更多限制，并且仅引起与其起源组织相关的细胞类型。然而，一些研究报告说，骨髓间充质基质细胞（MSC）能够转分化为神经细胞类型，有效跨越正常谱系限制边界。这样的报道是基于分化的MSC对神经相关蛋白的检测。为了评估人类成年MSC真正分化为神经系并确定供体样品之间同质性的可能性，我们使用了RT-PCR和免疫细胞化学来研究一系列神经相关mRNA和蛋白的基础表达。从4个供体获得的未分化MSC群体中的蛋白。结果表达分析表明，来自其他研究的几个常用标记基因，如巢蛋白，烯醇化酶2和微管相关蛋白1b（MAP1b）已由未分化的人类MSC表达。此外，某些神经相关转录因子的mRNA，例如Engrailed-1和Nurr1也被强烈表达。但是，可以鉴定出其他几种神经相关的mRNA（例如DRD2，烯醇酶2，NFL和MBP），但并非在所有供体样品中都可以鉴定出来。同样，仅在4个未分化供体hMSC样品中的2个中检测到了突触小泡相关的mRNA STX1A。更重要的是，每个供体样品均显示出独特的表达模式，表明标记物表达的显着变化。结论本研究强调了人类MSC样品中神经相关标志物表达的供体间变异性的存在，这一点以前没有描述过。这种与供体有关的异质性可能影响转分化方案的可重复性，并加剧了有关MSC分化能力的持续争议。因此，进一步的研究需要考虑在进行任何处理之前供体样品之间的差异，以及收获可能不适合移植策略的供体细胞的可能性。

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