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miR-145: An Important new Target for the Treatment of Diabetic Stroke?

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Review of “miR-145 Regulates Diabetes-Bone Marrow Stromal Cell-Induced Neurorestorative Effects in Diabetes Stroke Rats” from Stem Cells Translational Medicine by Stuart P. Atkinson

Ischemic stroke is of grave concern to type 1 diabetes (T1D) patients, as many diabetes symptoms contribute to poor stroke outcome [1, 2]. In non-diabetic stroke models, intravenous administration of healthy bone marrow mesenchymal stem cells (MSCs) represents a promising treatment modality [3]. This supports the use of patient-derived MSCs to treat stroke; however the application of MSCs derived from healthy patients actually worsened symptoms in a diabetic stroke model in a more recent study [4].

Now, researchers from the laboratory of Jieli Chen and Guiyun Cui have assessed whether MSCs derived from T1D rats (T1D-MSCs) could play a neurorestorative role in a diabetic stroke model, concentrating their study on their neuroprotective effect of miRNA145 (miR-145) inhibition [5]. Has this study uncovered an important new target for the treatment of diabetic stroke [6]?

In vitro analyses of T1D-MSCs in comparison to healthy MSCs demonstrated increased survival and proliferation coupled with decreased miR-145 expression. Additionally, T1D-MSC conditioned medium treatment of cultured primary cortical neurons increased capillary tube formation and axonal outgrowth. Encouraging findings!

Moving in vivo, systemic T1D-MSC treatment following induced stroke in T1DM rats mediated a significant improvement in neurological functional outcomes, increased vascular and white matter remodeling, and decreased blood-brain-barrier leakage. These improvements correlated with decreased miR-145 expression and increased expression of target genes (ABCA1 and IGFR1) which may be important for stroke treatment (Figure shows elevated expression following T1D MSC treatment [+DM-BMSCs] compared to control PBS treated mice [T1DM]).

The promise of an important new target for the treatment of diabetic stroke; exciting research! While healthy MSCs do more harm than good in diabetic stroke models, this study indicates that T1D-MSCs can promote neurorestorative effects via the downregulation of miR-145 expression. The authors note the probable involvement of other miRNAs and they hope to explore this likelihood in the near future. 

More surprises ahead; keep tuned to the Stem Cells Portal to hear all about their new and exciting findings!

References

  1. Yong M and Kaste M. Dynamic of hyperglycemia as a predictor of stroke outcome in the ECASS-II trial. Stroke 2008;39:2749-2755.
  2. Chen J, Cui X, Zacharek A, et al. White matter damage and the effect of matrix metalloproteinases in type 2 diabetic mice after stroke. Stroke 2011;42:445-452.
  3. Chen J, Li Y, Wang L, et al. Therapeutic benefit of intravenous administration of bone marrow stromal cells after cerebral ischemia in rats. Stroke 2001;32:1005-1011.
  4. Chen J, Ye X, Yan T, et al. Adverse effects of bone marrow stromal cell treatment of stroke in diabetic rats. Stroke 2011;42:3551-3558.
  5. Dharap A, Bowen K, Place R, et al. Transient focal ischemia induces extensive temporal changes in rat cerebral microRNAome. J Cereb Blood Flow Metab 2009;29:675-687.
  6. Cui C, Ye X, Chopp M, et al. miR-145 Regulates Diabetes-Bone Marrow Stromal Cell-Induced Neurorestorative Effects in Diabetes Stroke Rats. Stem Cells Translational Medicine 2016;5:1656-1667.