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CD133+Exosome Treatment Improves Cardiac Function after Stroke in Type 2 Diabetic Mice
Poornima Venkat1, Chengcheng Cui1, Zhili Chen1
1Department of Neurology, Henry Ford Hospital, Detroit, MI, 48202, USA.
Translational Stroke Research
|March 22, 2020
Summary
Exosomes from CD133+ cells (CD133+Exo) improve cardiac function in type 2 diabetes mellitus (T2DM) stroke mice by reducing inflammation and fibrosis. This therapy shows promise for managing post-stroke cardiac complications in diabetic patients.
Area of Science:
- Cardiovascular Research
- Regenerative Medicine
- Diabetes Complications
Background:
- Cardiac complications are frequent after stroke, with diabetes mellitus (T2DM) worsening cardiac injury.
- Existing treatments for post-stroke cardiac dysfunction in diabetic individuals are limited.
- Exosomes derived from specific stem cell populations are being investigated for therapeutic potential.
Purpose of the Study:
- To evaluate the efficacy of exosomes from human umbilical cord blood CD133+ cells (CD133+Exo) in improving cardiac function in a mouse model of type 2 diabetes mellitus (T2DM) with stroke.
- To investigate the underlying mechanisms of CD133+Exo's cardioprotective effects, including microRNA-126 (miR-126) expression, capillary density, and inflammatory markers.
Main Methods:
- Type 2 diabetes mellitus (T2DM) and non-diabetic mice underwent photothrombotic stroke or sham procedures.
- T2DM-stroke mice received intravenous injections of phosphate-buffered saline (PBS) or CD133+Exo.
- Cardiac function (echocardiography), cardiac histology (hypertrophy, fibrosis, capillary density), inflammatory markers, oxidative stress, and miR-126 expression were assessed 28 days post-stroke.
Main Results:
- CD133+Exo treatment significantly improved cardiac function in T2DM-stroke mice, evidenced by increased left ventricular ejection fraction (LVEF) and decreased left ventricular diastolic dimension (LVDD).
- Treatment reduced cardiac hypertrophy, interstitial fibrosis, M1 macrophage infiltration, and oxidative stress markers in T2DM-stroke mice.
- CD133+Exo treatment increased myocardial capillary density and upregulated miR-126 expression in the heart, while decreasing its target genes (Spred-1, VCAM, MCP1).
Conclusions:
- Exosomes derived from CD133+ cells (CD133+Exo) demonstrate significant cardioprotective effects in a mouse model of type 2 diabetes mellitus with stroke.
- The therapeutic benefits are likely mediated by increased miR-126 expression, enhanced myocardial capillary density, and reduced cardiac inflammation and fibrosis.
- CD133+Exo therapy represents a promising strategy for mitigating cardiac injury following stroke in diabetic patients.
