Abstract TMP112: CD133+Exosome Treatment Improves Neuro-cognitive and Cardiac Function after Stroke in Female Adult Type 2 Diabetic Mice

Background: Cardiac complications post-stroke are common, and diabetes exacerbates post-stroke cardiac injury. In this study, we tested whether treatment with exosomes harvested from human umbilical cord blood derived CD133+ cells (CD133+Exo) improve neuro-cognitive and cardiac function in female type 2 diabetes mellitus (T2DM) mice subjected to ischemic stroke. Methods: Female, adult non-DM and T2DM mice were randomized to: 1) Non-DM (n=6), 2) Non-DM-stroke (n=15), 3) T2DM (n=8), 4) T2DM-stroke (n=12) and 5) T2DM-stroke+Exo (n=13). CD133+Exo (20μg/200μl PBS, i.v.) was administered 3 days after stroke. Evaluation of neurological function (mNSS, adhesive removal test), cognitive function (novel object recognition (NOR) test, odor test) and cardiac function (echocardiography) was performed, and mice were sacrificed at 28 days after stroke. Results: Stroke induces severe neurological deficits and significant short-term and long-term memory deficits which were worse in T2DM mice compared to non-DM mice. CD133+Exo treatment in T2DM-stroke mice significantly improves neurological function and cognitive outcome indicated by improved discrimination index in NOR test and odor test compared to control T2DM-stroke mice. T2DM-stroke induces significant cardiac dysfunction indicated by reduced left ventricular ejection fraction (LVEF) and shortening fraction (LVSF) compared to T2DM-control and non-DM-stroke mice. CD133+Exo treatment significantly improves LVEF, LVSF and heart rate and reduces left ventricular dimension compared to T2DM-stroke mice. T2DM-stroke mice exhibit significantly increased cardiomyocyte hypertrophy, cardiac fibrosis and inflammation compared to T2DM-control and non-DM-stroke mice. Treatment of T2DM-stroke with CD133+Exo significantly reduced cardiomyocyte hypertrophy, cardiac fibrosis and inflammation compared to T2DM-stroke mice. T2DM-stroke increases while CD133+Exo treatment reduces expression of serum inflammatory factors such as MMP-2, DKK-1, CRP, VCAM, CXCL5 and Cystatin-C. Conclusions: In T2DM-stroke mice, CD133+Exo treatment significantly improves neurological, cognitive, and cardiac function, and reduces cardiac pathological remodeling compared to T2DM-stroke control mice.