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

17 Citations (Scopus)

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

Fingerprint

MicroRNAs
Mesenchymal Stromal Cells
Cell Movement
Therapeutics
Mesenchymal Stem Cell Transplantation
Cell Transplantation
Therapeutic Uses
Luciferases
Intravenous Infusions
Genes
Stem Cells
Down-Regulation
Polymerase Chain Reaction

Keywords

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

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy. / Hu, Xinyang; Chen, Panpan; Wu, Yan; Wang, Kan; Xu, Yinchuan; Chen, Han; Zhang, Ling; Wu, Rongrong; Webster, Keith A; Yu, Hong; Zhu, Wei; Wang, Jian'an.

In: Stem Cells, Vol. 34, No. 7, 01.07.2016, p. 1846-1858.

Research output: Contribution to journalArticle

Hu, X, Chen, P, Wu, Y, Wang, K, Xu, Y, Chen, H, Zhang, L, Wu, R, Webster, KA, Yu, H, Zhu, W & Wang, J 2016, 'MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy', Stem Cells, vol. 34, no. 7, pp. 1846-1858. https://doi.org/10.1002/stem.2391
Hu, Xinyang ; Chen, Panpan ; Wu, Yan ; Wang, Kan ; Xu, Yinchuan ; Chen, Han ; Zhang, Ling ; Wu, Rongrong ; Webster, Keith A ; Yu, Hong ; Zhu, Wei ; Wang, Jian'an. / MiR-211/STAT5A Signaling Modulates Migration of Mesenchymal Stem Cells to Improve its Therapeutic Efficacy. In: Stem Cells. 2016 ; Vol. 34, No. 7. pp. 1846-1858.
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AU - Zhang, Ling

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AU - Webster, Keith A

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