Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2.

Low osteogenic differentiation potential of placenta-derived mesenchymal stromal cells correlates with low expression of the transcription factors Runx2 and Twist2.
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胎盘来源的间充质基质细胞的低成骨分化潜力与转录因子 Runx2 和 Twist2 的低表达相关

DOI:
10.1089/scd.2012.0693
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发表时间:
2013
影响因子:
4
通讯作者:
Aicher WK
Aicher WK
中科院分区:
医学3区
文献类型:
--
作者:
Ulrich C;Rolauffs B;Abele H;Bonin M;Nieselt K;Hart ML;Aicher WK

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最近的研究表明,骨髓间充质间质细胞(bmMSC)与足月胎盘间充质间质细胞(pMSC)在成骨分化能力上存在差异。我们扩展了这些研究,并研究了两种细胞类型中参与骨代谢调节的因子的表达。为此,我们对MSC进行了体外扩增和表征。通过微阵列研究总转录组,并通过定量逆转录-聚合酶链反应、免疫细胞化学和流式细胞术研究选定基因的基因表达差异。我们报道了bmMSC和pMSC共同表达典型的谱系表面标记,包括CD73、CD90、CD105,以及缺乏CD14、CD34和CD45。然而,根据转录组分析,它们在590多个基因的表达上存在显著差异。骨代谢相关因子碱性磷酸酶(P<0.05)、骨胰素(P<0.05)、骨调节蛋白(P<0.05)、矮子相关转录因子2 (Runx2) (P<0.04)和WISP2 (P<0.05)在pMSC中的表达水平显著降低,而扭曲相关蛋白2 (Twist2) (P<0.0002)的表达水平显著升高。pMSC的成骨分化能力很低。组织化学染色显示,bmMSC的成脂分化更为突出,而bmMSC和pMSC的成软骨分化似乎没有差异。然而,在bmMSC中,过氧化物酶体增殖物激活受体γ -2 (ppar γ -2)和Sox9的表达和诱导分别参与早期脂肪形成和软骨形成。我们得出结论,尽管bmMSC和pMSC之间有许多相似之处,但在相同条件下扩增时,它们的体外分化潜力差异很大。因此,对于再生目的而言,MSC的选择可能会对治疗结果产生很大影响。
Recent studies indicated that mesenchymal stromal cells from bone marrow (bmMSC) differ in their osteogenic differentiation capacity compared to MSC from term placenta (pMSC). We extended these studies and investigated the expression of factors involved in regulation of bone metabolism in both cell types. To this end, MSC were expanded in vitro and characterized. The total transcriptome was investigated by microarrays, and for selected genes, the differences in gene expression were explored by quantitative reverse transcriptase-polymerase chain reaction, immunocytochemistry, and flow cytometry. We report that bmMSC and pMSC share expression of typical lineage surface markers, including CD73, CD90, CD105, and lack of CD14, CD34, and CD45. However, according to transcriptome analyses, they differ significantly in their expression of more than 590 genes. Factors involved in bone metabolism, including alkaline phosphatase (P<0.05), osteoglycin (P<0.05), osteomodulin (P<0.05), runt-related transcription factor 2 (Runx2) (P<0.04), and WISP2 (P<0.05), were expressed at significantly lower levels in pMSC, but twist-related protein 2 (Twist2) (P<0.0002) was expressed at significantly higher levels. The osteogenic differentiation capacity of pMSC was very low. The adipogenic differentiation was somewhat more prominent in bmMSC, while the chondrogenic differentiation seemed not to differ between bmMSC and pMSC, as determined by histochemical staining. However, expression and induction of peroxisome proliferator-activated receptor gamma-2 (PPARγ2) and Sox9, factors involved in early adipogenesis and chondrogenesis, respectively, were higher in bmMSC. We conclude that despite many similarities between bmMSC and pMSC, when expanded under identical conditions, they vary considerably with respect to their in vitro differentiation potential. For regenerative purposes, the choice of MSC may therefore influence the outcome of a treatment considerably.
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