MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy

Xinyang Hu, Panpan Chen, Yan Wu, Kan Wang, Yinchuan Xu, Han Chen, Ling Zhang, Rongrong Wu, Keith A Webster, Hong Yu, Wei Zhu, Jian'an Wang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Our previous study showed that the therapeutic effects of mesenchymal stem cells (MSCs) transplantation were improved by enhancing migration. MicroRNA-211 (miR-211) can modulate the migratory properties of some cell types by mechanisms that are not fully understood. This study was designed to investigate a possible role for miR-211 in MSC migration, and whether genetic manipulation of miR-211 in MSCs could be used to enhance its beneficial effects of cell transplantation. Transwell assays confirmed that MSCs migration of was significantly impaired by miR-211 knockdown but enhanced by miR-211 overexpression. MiR-211 overexpressing MSCs also exhibited significantly increased cell engraftment in the peri-infarct areas of female rat hearts 2 days after intravenous transplantation of male MSCs as shown by GFP tracking and SYR gene quantification. This conferred a significant decrease in infarct size and improved cardiac performance. By using a loss or gain of gene function approach, we demonstrated that miR-211 targeted STAT5A to modulate MSCs migration, possibly by interacting with MAPK signaling. Furthermore, the beneficial effects of miR-211 overexpression in MSCs were abolished by simultaneous overexpression of STAT5A whereas the negative effects of miR-211 silencing on MSC migration were rescued by simultaneous downregulation of STAT5A. Finally, using ChIP-PCR and luciferase assays, we provide novel evidence that STAT3 can directly bind to promoter elements that activate miR-211 expression. STAT3/miR-211/STAT5A signaling plays a key role in MSCs migration. Intravenous infusion of genetically modified miR-211 overexpressing MSCs conveys enhanced protection from adverse post-MI remodeling compared with unmodified MSCs. Stem Cells 2016;34:1846–1858.

Original languageEnglish (US)
Pages (from-to)1846-1858
Number of pages13
JournalStem Cells
Volume34
Issue number7
DOIs
StatePublished - Jul 1 2016

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Keywords

  • Mesenchymal stem cells
  • MicroRNA-211
  • Migration
  • Myocardial infarction
  • Retention
  • STAT5A

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Hu, X., Chen, P., Wu, Y., Wang, K., Xu, Y., Chen, H., Zhang, L., Wu, R., Webster, K. A., Yu, H., Zhu, W., & Wang, J. (2016). MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy. Stem Cells, 34(7), 1846-1858. https://doi.org/10.1002/stem.2391