Abstract 17148: Transplant of Smooth Muscle cell-Endothelial Progenitor Cell Bi-level Cell-sheet Attenuated Cardiac Dysfunction and Microvascular Disease in Diabetic Cardiomyopathy
Introduction: Diabetes mellitus (DM) is a risk factor for coronary artery disease and negatively impacts outcomes after CABG. Current treatments focus on macrorevascularization and neglect the microvascular disease typical of DM. We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets would improve the microvascular disease-induced ventricular dysfunction characteristic of diabetic cardiomyopathy (DMCM).
Methods and Results: Primary mesenchymal stem cells (MSCs) and EPCs were isolated from bone marrow of Wistar rats, and MSCs were transformed into SMCs by culture on a fibronectin-coated dish. SMCs topped with EPCs were detached from a temperature-responsive culture dish to create an SMC-EPC bi-level cell sheet. A DMCM model was induced with streptozocin. Within 3 weeks diabetic rat hearts were dilated, hypocontractile, and exhibited perivascular and interstitial fibrosis. Three weeks after induction of DM, 18 rats were randomized into 3 groups: control (no DM induction), untreated DMCM, and cell sheet-treated DMCM. Echocardiographic assessment 4 weeks after surgery demonstrated that cardiac function in the cell sheet-treated hearts was better than that of the untreated hearts with DMCM (Fig 1; p<0.0001). Cell sheets also halted adverse ventricular remodeling (Fig 1). Microvascular density was increased and interstitial fibrosis was reduced in the treated DMCM group compared with that of untreated DMCM (vascular density/mm2: treated 2570±166 vs untreated 1824±667 vs control 3095±93, p<0.01; and fibrosis(%): treated 1.21±0.26 vs untreated 2.18±0.52 vs control 1.02±0.24, p<0.01).
Conclusions: Tissue engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and extension of microvascular disease in diabetic hosts. This autologous, multilineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients. .
Author Disclosures: M. Kawamura: None. A.B. Goldstone: None. Y. Shudo: None. A.N. Steele: None. M. Hopkins: None. B. Edwards: None. J. Patel: None. C. Jensen: None. L.M. Stapleton: None. A. Eskandari: None. A.B. Ingason: None. Y.J. Woo: None.
- © 2016 by American Heart Association, Inc.