机构:[1]The Second School of Clinical Medical, Southern Medical University, Guangzhou, Guangdong 510515[2]Department of Hematology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences广东省人民医院[3]Department of Hematology, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080[4]Department of Hematology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000河北大学附属医院[5]Department ofHematology, South China University of Technology School of Medicine, Guangzhou, Guangdong 5100065, P.R. China
Mesenchymal stem cells (MSCs) derived from myelodysplastic syndromes (MDSs) have been demonstrated to accelerate the progression of MDS. However, whether the phenotype of MSCs derived from MDS (MDS-MSCs) may be reversed and serve as a potential target for the treatment of MDS remains unclear. The present study investigated the functional alternations of MDS-MSCs following in vitro decitabine-treatment. Primary MSCs were cultured from the bone marrow aspirates of 28 patients with MDS. The impact on the growth of MDS-MSCs treated with decitabine was analyzed using the MTT assay. Changes in the gene expression levels of runt related transcription factor 2 (RUNX2), Sp7 transcription factor (SP7), cyclin dependent kinase inhibitor 1A (CDKN1A) and CD274 in MDS-MSCs following treatment with decitabine were analyzed by reverse transcription-quantitative polymerase chain reaction. The effects of decitabine on apoptosis and the cell cycle were examined using flow cytometry. The effect of decitabine on the immune regulation of MDS-MSCs was tested by the co-culture of MSCs with activated T cells in vitro. The results revealed that proliferation, apoptosis and the mRNA expression levels of RUNX2 and SP7 in MDS-MSCs did not significantly change following treatment with decitabine compared with control MDS-MSCs. However, treatment with decitabine resulted in a smaller population of cells in the G1 phase and an increase in the number of cells in the G2/M phase compared with control MDS-MSCs. This change was associated with decreased expression of CDKN1A in cells treated with decitabine compared with control cells. Notably, the ability of MDS-MSCs treated with decitabine to induce the differentiation of T cells into regulatory T cells was significantly reduced compared with control MDS-MSCs. This was associated with a decreased expression of CD274 in MDS-MSCs treated with decitabine compared with control MDS-MSCs. In conclusion, the phenotype of MSCs derived from patients with MDS was partially reversed by treatment with decitabine, presenting a potential therapeutic intervention.
基金:
National Natural Science Foundation of China [81500102]; Science and Technology Planning Project of Guangdong [2014B020212009, 2014B020226002, 2015B020227003, 2015B020226001, 2017B020230004]; Science and Technology Planning Project of Guangzhou [201803040005, 201803040011, 201400000003-4]; Natural Science Foundation of Guangdong [S2013030013305]
第一作者机构:[1]The Second School of Clinical Medical, Southern Medical University, Guangzhou, Guangdong 510515[2]Department of Hematology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences[3]Department of Hematology, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080[4]Department of Hematology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000
共同第一作者:
通讯作者:
通讯机构:[1]The Second School of Clinical Medical, Southern Medical University, Guangzhou, Guangdong 510515[2]Department of Hematology, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences[3]Department of Hematology, Guangdong Geriatrics Institute, Guangzhou, Guangdong 510080[5]Department ofHematology, South China University of Technology School of Medicine, Guangzhou, Guangdong 5100065, P.R. China[*1]Department of Hematology,Guangdong Provincial People's Hospital and Guangdong Academyof Medical Sciences, 106 Zhongshan Er Road, Guangzhou,Guangdong 510080, P.R. China
推荐引用方式(GB/T 7714):
Pang Yanbin,Geng Suxia,Zhang Hongyang,et al.Phenotype of mesenchymal stem cells from patients with myelodyplastic syndrome maybe partly modulated by decitabine[J].ONCOLOGY LETTERS.2019,18(5):4457-4466.doi:10.3892/ol.2019.10788.
APA:
Pang, Yanbin,Geng, Suxia,Zhang, Hongyang,Lai, Peilong,Liao, Pengjun...&Du, Xin.(2019).Phenotype of mesenchymal stem cells from patients with myelodyplastic syndrome maybe partly modulated by decitabine.ONCOLOGY LETTERS,18,(5)
MLA:
Pang, Yanbin,et al."Phenotype of mesenchymal stem cells from patients with myelodyplastic syndrome maybe partly modulated by decitabine".ONCOLOGY LETTERS 18..5(2019):4457-4466