Effects of transforming growth factor-beta 1 and ascorbic acid on differentiation of human bone-marrow-derived mesenchymal stem cells into smooth muscle cell lineage

Effects of transforming growth factor-beta 1 and ascorbic acid on differentiation of human bone-marrow-derived mesenchymal stem cells into smooth muscle cell lineage
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DOI:
10.1007/s00441-008-0654-0
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发表时间:
2008-09-01
影响因子:
3.6
通讯作者:
Ueda, Yuichi
Ueda, Yuichi
中科院分区:
生物学3区
文献类型:
--
作者:
Narita, Yuji;Yamawaki, Aika;Ueda, Yuichi

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骨髓间充质干细胞(MSCs)可以分化为包括平滑肌细胞(SMC)在内的多种细胞类型。我们试图证明,在用转化生长因子-β 1(TGF-β 1)和抗坏血酸(AA)处理后,人骨髓来源的MSC分化成SMC谱系用于组织工程。对MSC进行SMC特异性基因(α平滑肌肌动蛋白、h1-钙调蛋白和SM 22 α)表达的定量聚合酶链反应,MSC与不同浓度的TGF-β 1或AA一起培养。TGF-β 1具有以剂量依赖性方式上调SMC特异性基因表达的趋势。30 μ M AA显著上调SM 22 α的表达。我们还研究了TGF-β 1和AA对向SMC分化的累加效应,并将这种效应与包括血小板衍生生长因子BB(PDGF-BB)在内的其他因子的效应进行了比较。除了SMC特异性基因表达外,当TGF-β 1和AA一起使用时,SMC特异性蛋白质比单独使用时增加了2至4倍。PDGF不增加SMC特异性标志物的表达。TGF-β 1和AA共同培养的MSCs不能分化为成骨细胞和脂肪细胞。这些结果表明,TGF-β 1和AA的组合对于MSC分化为SMC用于组织工程是有用的。
Bone-marrow-derived mesenchymal stem cells (MSCs) can differentiate into a variety of cell types including smooth muscle cells (SMCs). We have attempted to demonstrate that, following treatment with transforming growth factor-beta 1 (TGF-beta 1) and ascorbic acid (AA), human bone-marrow-derived MSCs differentiate into the SMC lineage for use in tissue engineering. Quantitative polymerase chain reaction for SMC-specific gene (alpha smooth muscle actin, h1-calponin, and SM22 alpha) expression was performed on MSCs, which were cultured with various concentrations of TGF-beta 1 or AA. TGF-beta 1 had a tendency to up-regulate the expression of SMC-specific genes in a dose-dependent manner. The expression of SM22 alpha was significantly up-regulated by 30 mu M AA. We also investigated the additive effect of TGF-beta 1 and AA for differentiation into SMCs and compared this effect with that of other factors including platelet-derived growth factor BB (PDGF-BB). In addition to SMC-specific gene expression, SMC-specific proteins increased by two to four times when TGF-beta 1 and AA were used together compared with their administration alone. PDGF did not increase the expression of SMC-specific markers. MSCs cultured with TGF-beta 1 and AA did not differentiate into osteoblasts and adipocytes. These results suggest that a combination of TGF-beta 1 and AA is useful for the differentiation of MSCs into SMCs for use in tissue engineering.