In silicomechanics and TGF-ß expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction

Abstract

AbstractPurposeBiomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the therapeutic benefits require further clarification. This study aimed to assess the deformation and resulting transforming growth factor β (TGF-β) expression of stem cells injected with the biomaterial into the infarcted heart.MethodsA microstructural finite element model of a mid-wall infarcted myocardial region was developed fromex vivomicrocomputed tomography data of a rat heart with left ventricular infarct and intramyocardial biomaterial injectate. Nine cells were numerically seeded in the injectate of the microstructural model. The microstructural and a previously developed biventricular finite element model of the same rat heart were used to quantify the deformation of the cells during a cardiac cycle for a biomaterial elastic modulus (Einj) ranging between 4.1 and 405,900 kPa. The cellular TGF-β expression was determined with a mathematical relationship of deformation and TGF-β expression developed from existing experimental data and single-cell finite element analysis.ResultsThe transplanted cells’ deformation and TGF-β expression were largest for Einj= 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. Cell deformation and TGF-β expression were more sensitive to Einjchanges for softer (Einj≤ 738 kPa) than stiffer biomaterials.ConclusionsCombining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The approach offers a broader scope forin silicoinvestigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.