Delivery of progenitor cells with injectable shear-thinning hydrogel maintains geometry and normalizes strain to stabilize cardiac function after ischemia
| Autor: | Chantel M. Venkataraman, Ann C. Gaffey, Susan M. Schultz, Pavan Atluri, Alen Trubelja, Minna H. Chen, Jason A. Burdick, Chandra M. Sehgal, Jennifer J. Chung, Carol W. Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
Pulmonary and Respiratory Medicine Cardiac function curve medicine.medical_specialty Cell Survival Myocardial Infarction Ischemia Neovascularization Physiologic 030204 cardiovascular system & hematology Endothelial progenitor cell Ventricular Function Left Article Injections Cell therapy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tensile Strength Internal medicine Hyaluronic acid medicine Animals Myocardial infarction Hyaluronic Acid Rats Wistar Progenitor cell Cells Cultured Endothelial Progenitor Cells Ventricular Remodeling business.industry Myocardium Stem Cells Graft Survival Hemodynamics Hydrogels Recovery of Function medicine.disease Biomechanical Phenomena Disease Models Animal medicine.anatomical_structure 030228 respiratory system chemistry Ventricle Cardiology Surgery Stress Mechanical Cardiology and Cardiovascular Medicine business Stem Cell Transplantation |
| Zdroj: | J Thorac Cardiovasc Surg |
| Popis: | Objectives The ventricle undergoes adverse remodeling after myocardial infarction, resulting in abnormal biomechanics and decreased function. We hypothesize that tissue-engineered therapy could minimize postischemic remodeling through mechanical stress reduction and retention of tensile myocardial properties due to improved endothelial progenitor cell retention and intrinsic biomechanical properties of the hyaluronic acid shear-thinning gel. Methods Endothelial progenitor cells were harvested from adult Wistar rats and resuspended in shear-thinning gel. The constructs were injected at the border zone of ischemic rat myocardium in an acute model of myocardial infarction. Myocardial remodeling, tensile properties, and hemodynamic function were analyzed: control (phosphate-buffered saline), endothelial progenitor cells, shear-thinning gel, and shear-thinning gel + endothelial progenitor cells. Novel high-resolution, high-sensitivity ultrasound with speckle tracking allowed for global strain analysis. Uniaxial testing assessed tensile biomechanical properties. Results Shear-thinning gel + endothelial progenitor cell injection significantly increased engraftment and retention of the endothelial progenitor cells within the myocardium compared with endothelial progenitor cells alone. With the use of strain echocardiography, a significant improvement in left ventricular ejection fraction was noted in the shear-thinning gel + endothelial progenitor cell cohort compared with control (69.5% ± 10.8% vs 40.1% ± 4.6%, P = .04). A significant normalization of myocardial longitudinal displacement with subsequent stabilization of myocardial velocity with shear-thinning gel + endothelial progenitor cell therapy compared with control was also evident (0.84 + 0.3 cm/s vs 0.11 ± 0.01 cm/s, P = .03). A significantly positive and higher myocardial strain was observed in shear-thinning gel + endothelial progenitor cell (4.5% ± 0.45%) compared with shear-thinning gel (3.7% ± 0.24%), endothelial progenitor cell (3.5% ± 0.97%), and control (8.6% ± 0.3%, P = .05). A resultant reduction in dynamic stiffness was noted in the shear-thinning gel + endothelial progenitor cell cohort. Conclusions This novel injectable shear-thinning hyaluronic acid hydrogel demonstrates stabilization of border zone myocardium with reduction in adverse myocardial remodeling and preservation of myocardial biomechanics. The cellular construct provides a normalization of strain measurements and reduces left ventricular dilatation, thus resulting in improvement of left ventricular function. |
| Databáze: | OpenAIRE |
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