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

<italic>Objective</italic>. The study aim to investigate the role of microRNA-155 (miR-155) on the immunoregulatory function of bone marrow mesenchymal stem cells (MSCs).<italic> Methods</italic>. MSCs were isolated from 2-week-old Sprague-Dawley rats and identified by flow cytometry using anti-CD29...

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Publicado en:BioMed Research International Vol. 2018; pp. 1 - 11
Autores principales: Zhang, Xiaoming, Hua, Fei, Yang, Ziying, Chen, Yueqiu, Teng, Xiaomei, Huang, Haoyue, Zhao, Yunfeng, Shen, Zhenya
Formato: pictorial research tables/charts Journal Article
Publicado: Wiley-Blackwell 5/8/2018
Acceso en línea:Ver este registro en EBSCOhost
Descripción
Sumario:<italic>Objective</italic>. The study aim to investigate the role of microRNA-155 (miR-155) on the immunoregulatory function of bone marrow mesenchymal stem cells (MSCs).<italic> Methods</italic>. 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.<italic> Results</italic>. 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<italic> Tbx21</italic>,<italic> Rorc,</italic> and<italic> SOCS1</italic>, while the expression of<italic> Gata3</italic> and<italic> Foxp3</italic> was increased. In contrast to the downregulation of the aforementioned genes, miR155-inhibitor-transfected MSCs resulted in upregulation of<italic> Tbx21</italic>,<italic> Rorc</italic>, and<italic> SOCS1</italic> expression levels and inhibition of<italic> Gata3</italic> and<italic> Foxp3</italic>. 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.).<italic> Conclusion</italic>. 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.