Department of Hematology, The Oncology Hospital of Tianjin Medical University, Tianjin, P.R. China.
PLoS One. 2012;7(9):e45675. doi: 10.1371/journal.pone.0045675. Epub 2012 Sep 21.
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.
骨髓增生异常综合征（MDS）是一组进行性、克隆性、肿瘤性骨髓疾病，其特征为造血干细胞失调和免疫系统异常。间充质干细胞（MSC）在展示出免疫调节作用后引起了更多关注。然而，MDS 骨髓来源的 MSC（MDS-MSC）的免疫调节功能仍未得到明确界定。此外，低危和高危 MDS-MSC 之间的调节功能是否存在差异尚不清楚。在这项研究中，我们从 MDS 患者的骨髓中获得和扩增 MSC。我们的结果表明，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 与 TGF-β1 增加、凋亡增加、免疫抑制率增加和造血支持能力差有关。此外，我们的结果发现高危 MDS-MSC 和低危 MDS-MSC 之间 CD4+CD25+Foxp3+Tregs 的诱导率存在很大差异。与高危 MDS-MSC 相比，低危 MDS-MSC 的 CD4+CD25+Foxp3+Tregs 诱导率较低。最后，我们发现基于敲低研究，MDS-MSC 衍生的 TGF-β1 是导致 CD4+CD25+Foxp3+Tregs 增加的主要原因。这些结果阐明了 MSC 在低危和高危 MDS 中的不同免疫调节作用，这对于理解 MDS 的发病机制以及为 MDS 的治疗开发新型免疫调节策略可能很重要。
