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- Title
Mesenchymal stem cell transplantation for the infarcted heart: therapeutic potential for insulin resistance beyond the heart.
- Authors
Hughey, Curtis C.; Lianli Ma; James, Freyja D.; Bracy, Deanna P.; Wang, Zhizhang; Wasserman, David H.; Rottman, Jeffrey N.; Hittel, Dustin S.; Shearer, Jane
- Abstract
Background: This study aimed to evaluate the efficacy of mesenchymal stem cell (MSC) transplantation to mitigate abnormalities in cardiac-specific and systemic metabolism mediated by a combination of a myocardial infarction and diet-induced insulin resistance. Methods: C57BL/6 mice were high-fat fed for eight weeks prior to induction of a myocardial infarction via chronic ligation of the left anterior descending coronary artery. MSCs were administered directly after myocardial infarction induction through a single intramyocardial injection. Echocardiography was performed prior to the myocardial infarction as well as seven and 28 days post-myocardial infarction. Hyperinsulinemic-euglycemic clamps coupled with 2-[14C]deoxyglucose were employed 36 days post-myocardial infarction (13 weeks of high-fat feeding) to assess systemic insulin sensitivity and insulin-mediated, tissue-specific glucose uptake in the conscious, unrestrained mouse. High-resolution respirometry was utilized to evaluate cardiac mitochondrial function in saponinpermeabilized cardiac fibers. Results: MSC administration minimized the decline in ejection fraction following the myocardial infarction. The greater systolic function in MSC-treated mice was associated with increased in vivo cardiac glucose uptake and enhanced mitochondrial oxidative phosphorylation efficiency. MSC therapy promoted reductions in fasting arterial glucose and fatty acid concentrations. Additionally, glucose uptake in peripheral tissues including skeletal muscle and adipose tissue was elevated in MSC-treated mice. Enhanced glucose uptake in these tissues was associated with improved insulin signalling as assessed by Akt phosphorylation and prevention of a decline in GLUT4 often associated with high-fat feeding. Conclusions: These studies provide insight into the utility of MSC transplantation as a metabolic therapy that extends beyond the heart exerting beneficial systemic effects on insulin action.
- Subjects
MESENCHYMAL stem cells; TREATMENT effectiveness; CELL transplantation; HEART abnormalities; MYOCARDIAL infarction treatment; INSULIN resistance; ECHOCARDIOGRAPHY; GENETICS; THERAPEUTICS
- Publication
Cardiovascular Diabetology, 2013, Vol 12, Issue 1, p1
- ISSN
1475-2840
- Publication type
Article
- DOI
10.1186/1475-2840-12-128