Tissue-engineered smooth muscle cell and endothelial progenitor cell bi-level cell sheets prevent progression of cardiac dysfunction, microvascular dysfunction, and interstitial fibrosis in a rodent model of type 1 diabetes-induced cardiomyopathy

Cardiovascular Diabetology

Original Investigation

Bryan B. Edwards¹  Hanjay Wang¹  Lyndsay M. Stapleton¹  Michael J. Paulsen¹  Vi N. Truong¹  Y. Joseph Woo¹  Anahita Eskandari¹  Arnar B. Ingason¹  Kevin J. Jaatinen¹  Andrew B. Goldstone¹  Amanda N. Steele¹  Masashi Kawamura²  Yasuhiro Shudo²  Yoshiki Sawa³  Shigeru Miyagawa³ 

[1] Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, 94305, Stanford, CA, USA;Department of Cardiothoracic Surgery, Stanford University School of Medicine, 300 Pasteur Drive, 94305, Stanford, CA, USA;Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, 565-0871, Suita, Japan;Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, 565-0871, Suita, Japan;

关键词: Diabetic cardiomyopathy;    Tissue engineering;    Cell therapy;   

DOI  :  10.1186/s12933-017-0625-4

 received in 2017-07-26, accepted in 2017-10-24,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundDiabetes mellitus is a risk factor for coronary artery disease and diabetic cardiomyopathy, and adversely impacts outcomes following coronary artery bypass grafting. Current treatments focus on macro-revascularization and neglect the microvascular disease typical of diabetes mellitus-induced cardiomyopathy (DMCM). We hypothesized that engineered smooth muscle cell (SMC)-endothelial progenitor cell (EPC) bi-level cell sheets could improve ventricular dysfunction in DMCM.MethodsPrimary mesenchymal stem cells (MSCs) and EPCs were isolated from the bone marrow of Wistar rats, and MSCs were differentiated into SMCs by culturing 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 by intraperitoneal streptozotocin injection. Four weeks after induction, rats were randomized into 3 groups: control (no DMCM induction), untreated DMCM, and treated DMCM (cell sheet transplant covering the anterior surface of the left ventricle).ResultsSMC-EPC cell sheet therapy preserved cardiac function and halted adverse ventricular remodeling, as demonstrated by echocardiography and cardiac magnetic resonance imaging at 8 weeks after DMCM induction. Myocardial contrast echocardiography demonstrated that myocardial perfusion and microvascular function were preserved in the treatment group compared with untreated animals. Histological analysis demonstrated decreased interstitial fibrosis and increased microvascular density in the SMC-EPC cell sheet-treated group.ConclusionsTreatment of DMCM with tissue-engineered SMC-EPC bi-level cell sheets prevented cardiac dysfunction and microvascular disease associated with DMCM. This multi-lineage cellular therapy is a novel, translatable approach to improve microvascular disease and prevent heart failure in diabetic patients.

【 授权许可】

CC BY   
© The Author(s) 2017