The different immunoregulatory functions of mesenchymal stem cells in patients with low-risk or high-risk myelodysplastic syndromes.
The different immunoregulatory functions of mesenchymal stem cells in patients with low-risk or high-risk myelodysplastic syndromes.
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间充质干细胞在低危或高危骨髓增生异常综合征患者中的不同免疫调节功能
DOI：
10.1371/journal.pone.0045675
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Zou P
中科院分区：
文献类型：
--
作者：
Zhao Z;Wang Z;Li Q;Li W;You Y;Zou P
骨髓增生异常综合征（MDS）是一组进展性、克隆性、肿瘤性骨髓疾病，其特征为造血干细胞失调以及免疫系统异常。间充质干细胞（MSC）在被证实具有免疫调节作用后受到了更多关注。然而，MDS骨髓来源的间充质干细胞（MDS - MSC）的免疫调节功能仍不明确。此外，低危和高危MDS - MSC之间在调节功能上是否存在差异也不清楚。在本研究中，我们从MDS患者的骨髓中获取并扩增间充质干细胞。我们的结果显示，低危和高危MDS - MSC之间的免疫调节功能存在显著差异。与低危MDS - MSC相比，高危MDS - MSC伴有转化生长因子-β1（TGF - β1）增加、细胞凋亡增多、免疫抑制率更高以及造血支持能力较差的情况。此外，我们的结果发现，高危MDS - MSC和低危MDS - MSC之间诱导产生CD4 + CD25 + Foxp3 +调节性T细胞（Tregs）的比率存在很大差异。与高危MDS - MSC相比，低危MDS - MSC诱导产生CD4 + CD25 + Foxp3 + Tregs的比率更低。最后，基于基因敲低研究，我们发现MDS - MSC产生的TGF - β1在很大程度上导致了CD4 + CD25 + Foxp3 + Tregs的增加。这些结果阐明了间充质干细胞在低危和高危MDS中不同的免疫调节作用，这对于理解MDS的发病机制以及开发治疗MDS的新型免疫调节策略可能具有重要意义。
Myelodysplastic syndrome (MDS) are a group of progressive, clonal, neoplastic bone marrow disorders characterized by hematopoietic stem cell dysregulation and abnormalities in the immune system. Mesenchymal stem cells (MSC) have gained further interests after the demonstration of an immunoregulatory role. Nevertheless, the immunoregulatory function of MDS bone marrow derived MSC (MDS-MSC) remains poorly defined. In addition, it is not clear whether there are differences in the regulatory functions between low-risk and high-risk MDS-MSC. In this study, we obtain and expand MSC from bone marrow of patients with MDS. Our results show that there are significant differences in the immunoregulatory functions between low-risk and high-risk MDS-MSC. Compare to low-risk MDS-MSC, high-risk MDS-MSC is associated with the presence of increased TGF-β1, higher apoptosis, higher immunosuppressive rate and a poor ability of hematopoietic support. In addition, our results find that there are great differences in the CD4+CD25+Foxp3+Tregs inducible rate between high-risk MDS-MSC and low-risk MDS-MSC. Compared to high-risk MDS-MSC, the inducible rate of CD4+CD25+Foxp3+Tregs of low-risk MDS-MSC is lower. At last, we find that MDS-MSC derived TGF-β1 is largely responsible for the increase in CD4+CD25+Foxp3+Tregs based on knockdown studies. These results elucidate the different immunoregulatory role of MSC in low-risk and high-risk MDS, which may be important for understand the pathogenesis of MDS and the development of novel immunomodulatory strategies for the treatment of MDS.
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影响因子：
4
作者：
Klaus, Mirjam;Stavroulaki, Emily;Papadaki, Helen A.
通讯作者：
Papadaki, Helen A.
影响因子：
4.4
作者：
Patel, Shyam A.;Meyer, Justin R.;Rameshwar, Pranela
通讯作者：
Rameshwar, Pranela
DOI：
10.1196/annals.1386.024
发表时间：
2006-01-01
期刊：
ESTROGENS AND HUMAN DISEASES
影响因子：
--
作者：
Buck, Miriam B.;Knabbe, Cornelius
通讯作者：
Knabbe, Cornelius
影响因子：
2.6
作者：
Guo, H;Fang, BJ;Zhao, RCH
通讯作者：
Zhao, RCH
影响因子：
6.2
作者：
Tse, WT;Pendleton, JD;Guinan, EC
通讯作者：
Guinan, EC