In silicomechanics and TGF-ß expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction
التفاصيل البيبلوغرافية
العنوان:
In silicomechanics and TGF-ß expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction
Biomaterial and stem cell delivery are promising approaches to treating myocardial infarction. However, the mechanical and biochemical mechanisms underlying the observed therapeutic benefits require further clarification. This computational study aimed to assess deformation and resulting transforming growth factor β (TGF-β) expression of stem cells injected with the biomaterial into the infarcted heart. A microstructural finite element model of a mid-wall equatorial 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. Deformation and TGF-β expression of the transplanted cells were largest at Einjof 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. Combining the microstructural and biventricular finite element models enables quantifying micromechanics and signalling of transplanted cells in the heart. The platform offers broader scope forin silicoinvestigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.
