Georgi Nicole, Taipaleenmaki Hanna, Raiss Christian C, Groen Nathalie, Portalska Karolina Janaeczek, van Blitterswijk Clemens, de Boer Jan, Post Janine N, van Wijnen Andre J, Karperien Marcel
1 Department of Developmental BioEngineering, Faculty of Science and Technology, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente , Enschede, the Netherlands .
2 Heisenberg-Group for Molecular Skeletal Biology, Department of Trauma-, Hand- and Reconstructive Surgery, University Medical Center Hamburg-Eppendorf , Hamburg, Germany .
Stem Cells Dev. 2015 Aug 15;24(16):1946-55. doi: 10.1089/scd.2014.0534. Epub 2015 Jun 17.
The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Since the differentiation potential of hMSCs differs between donors, it is necessary to establish biomarkers for the identification of donors with high differentiation potential. In this study, we show that microRNA (miRNA) expression levels are effective for distinguishing donors with high differentiation potential from low differentiation potential. Twenty hMSC donors were initially tested for marker expression and differentiation potential. In particular, the chondrogenic differentiation potential was evaluated on the basis of histological matrix formation, mRNA expression levels of chondrogenic marker genes, and quantitative glycosaminoglycan deposition. Three donors out of twenty were identified as donors with high chondrogenic potential, whereas nine showed moderate and eight showed low chondrogenic potential. Expression profiles of miRNAs involved in chondrogenesis and cartilage homeostasis were used for the distinction between high-performance hMSCs and low-performance hMSCs. Global mRNA expression profiles of the donors before the onset of chondrogenic differentiation revealed minor differences in gene expression between low and high chondrogenic performers. However, analysis of miRNA expression during a 7-day differentiation period identified miR-210 and miR-630 as positive regulators of chondrogenesis. In contrast, miR-181 and miR-34a, which are negative regulators of chondrogenesis, were upregulated during differentiation in low-performing donors. In conclusion, profiling of hMSC donors for a specific panel of miRNAs may have a prognostic value for selecting donors with high differentiation potential to improve hMSC-based strategies for tissue regeneration.
人间充质基质/干细胞（hMSCs）分化为各种间充质细胞谱系的能力使其成为用于组织修复策略的有前景的细胞来源。由于hMSCs的分化潜能在不同供体之间存在差异，因此有必要建立生物标志物以识别具有高分化潜能的供体。在本研究中，我们表明微小RNA（miRNA）表达水平可有效区分高分化潜能供体和低分化潜能供体。最初对20名hMSC供体进行了标志物表达和分化潜能测试。特别是，基于组织学基质形成、软骨生成标志物基因的mRNA表达水平以及定量糖胺聚糖沉积来评估软骨生成分化潜能。20名供体中有3名被鉴定为具有高软骨生成潜能的供体，而9名表现为中等软骨生成潜能，8名表现为低软骨生成潜能。参与软骨生成和软骨稳态的miRNA表达谱用于区分高性能hMSCs和低性能hMSCs。软骨生成分化开始前供体的整体mRNA表达谱显示，低软骨生成能力者和高软骨生成能力者之间在基因表达上存在微小差异。然而，对7天分化期内miRNA表达的分析确定miR-210和miR-630为软骨生成的正调节因子。相反，作为软骨生成负调节因子的miR-181和miR-34a在低性能供体的分化过程中上调。总之，对特定miRNA组进行hMSC供体分析可能对选择具有高分化潜能的供体具有预后价值，以改善基于hMSC的组织再生策略。
