Enhancement of Immunoregulatory Function of Modified Bone Marrow Mesenchymal Stem Cells by Targeting SOCS1

• Published in: BioMed research international Vol. 2018; no. 2018; pp. 1 - 10
• Main Authors: Shen, Zhenya, Huang, Haoyue, Teng, Xiaomei, Chen, Yueqiu, Yang, Ziying, Hua, Fei, Zhang, Xiaoming, Zhao, Yunfeng
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; Hindawi Limited
• Subjects: Animals; Antibodies; Antigens, CD - metabolism; Apoptosis; Biomedical research; Bone marrow; Bone Marrow Cells - metabolism; CD29 antigen; CD34 antigen; CD4 antigen; CD44 antigen; CD45 antigen; Cell Differentiation - physiology; Cells, Cultured; Coculture Techniques; Cytokines; Dendritic cells; Differentiation; Flow cytometry; Forkhead Transcription Factors - metabolism; Foxp3 protein; GATA-3 protein; GATA3 Transcription Factor - metabolism; Gene expression; Helper cells; Identification methods; Immunologic Factors - metabolism; Immunology; Immunoregulation; Inhibitors; Laboratory animals; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal stem cells; Mesenchymal Stem Cells - metabolism; Mesenchyme; MicroRNAs; MicroRNAs - metabolism; miRNA; Proteins; Rats; Rats, Sprague-Dawley; Rheumatoid arthritis; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Rodents; Spleen; Stem cell transplantation; Stem cells; Suppressor of Cytokine Signaling 1 Protein - metabolism; T-Box Domain Proteins - metabolism; T-Lymphocytes, Helper-Inducer; T-Lymphocytes, Regulatory - metabolism; Target detection; Transcription factors; Tumor necrosis factor-TNF; United States > US; China
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2018/3530647

Objective. The study aim to investigate the role of microRNA-155 (miR-155) on the immunoregulatory function of bone marrow mesenchymal stem cells (MSCs). Methods. MSCs were isolated from 2-week-old Sprague-Dawley rats and identified by flow cytometry using anti-CD29, anti-CD44, anti-CD34, and anti-CD45 antibodies. MSCs were transfected with miR155-mimics, miR155-inhibitor, and control oligos, respectively, and then cocultured with spleen mononuclear cells (SMCs). The mRNA levels of Th1, Th2, Th17, and Treg cell-specific transcription factors (Tbx21, Gata3, Rorc, and Foxp3, resp.) and the miR-155 target gene SOCS1 were detected by quantitative real-time PCR (qPCR) in SMCs. The proportion of CD4+ FOXP3+ Treg cells was detected by flow cytometry. In addition, the effects of MSCs transfected with miR-155 on the migration of rat SMCs were investigated by transwell chamber. Results. CD29 and CD44 were expressed in MSCs, while CD34 and CD45 were negative. The percentage of CD4+ FOXP3+ Treg cells in the SMC population was significantly higher compared with that noted in SMCs control group (p<0.001) following 72 hours of coculture with miR155-mimics-transfected SMCs. In contrast, the percentage of CD4+ FOXP3+ Treg cells in the SMCs cocultured with miR155-inhibitor-transfected MSCs was significantly lower compared with that noted in SMCs control group (p<0.001). MiR155-mimics-transfected MSCs inhibited the expression of Tbx21, Rorc, and SOCS1, while the expression of Gata3 and Foxp3 was increased. In contrast to the downregulation of the aforementioned genes, miR155-inhibitor-transfected MSCs resulted in upregulation of Tbx21, Rorc, and SOCS1 expression levels and inhibition of Gata3 and Foxp3. In the transwell assay, miR155-mimics-transfected MSCs exhibited lower levels of SMCs migration, while the miR155-inhibitor-transfected MSCs demonstrated significantly higher levels of migration, compared with the blank control group (p<0.01, resp.). Conclusion. miR-155 favors the differentiation of T cells into Th2 and Treg cells in MSCs, while it inhibits the differentiation to Th1 and Th17 cells.