Nagawa, J. | Search bioRxiv

bioRxiv2023

In silico mechanics and TGF-β expression of stem cells intramyocardially transplanted with a biomaterial injectate for treatment of myocardial infarction

PurposeBiomaterial 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 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 from ex vivo microcomputed 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. ResultsThe transplanted cells deformation was largest for Einj = 7.4 kPa, matching that of the cells, and decreased for an increase and decrease in Einj. The cell deformation was more sensitive to Einj changes 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 for in silico investigations of biomaterial and cell therapies for myocardial infarction and other cardiac pathologies.

bioengineering↗

bioRxiv2022

Effect of paclitaxel treatment on cellular mechanics and morphology of human oesophageal squamous cell carcinoma of South African origin in 2D and 3D environments

During chemotherapy, structural and mechanical changes in malignant cells have been observed in several cancers, including leukaemia and pancreatic and prostate cancer. Such cellular changes may act as physical biomarkers for chemoresistance and cancer recurrence. This study aimed to determine how exposure to paclitaxel affects the intracellular stiffness of human oesophageal cancer of South African origin in vitro. A human oesophageal squamous cell carcinoma cell line WHCO1 was cultured on glass substrates (2D) and in collagen gels (3D) and exposed to paclitaxel for up to 48 hours. Cellular morphology and stiffness were assessed with confocal microscopy, visually aided morpho-phenotyping image recognition, and mitochondrial particle tracking microrheology at 24 and 48 hours. In the 2D environment, the intracellular stiffness was higher for the paclitaxel-treated than for untreated cells at 24 and 48 hours. In the 3D environment, the paclitaxel-treated cells were stiffer than the untreated cells at 24 hours, but no statistically significant differences in stiffness were observed at 48 hours. In 2D, paclitaxel-treated cells were significantly larger at 24 and 48 hours and more circular at 24 but not at 48 hours than the untreated controls. In 3D, there were no significant morphological differences between treated and untreated cells. The distribution of cell shapes was not statistically significant different across the different treatment conditions in 2D and 3D environments. Future studies with patient-derived primary cancer cells and prolonged drug exposure will help identify physical cellular biomarkers to detect chemoresistance onset and assess therapy effectiveness in oesophageal cancer patients. InsightMechanical changes in cancer cells by chemotherapeutic drugs exposure offer possible physical biomarkers for chemoresistance and cancer recurrence. This study on human oesophageal squamous cell carcinoma indicated that in vitro paclitaxel treatment induced stiffening and enlarging of malignant cells in two-dimensional environments at 24 and 48 hours. In physiologically more relevant three-dimensional collagen matrices the paclitaxel treatment led to cellular stiffening at 24 hours but softening thereafter, without significant changes in cellular size at any time. The outcomes need to be confirmed in future studies with prolonged drug exposure and patient-derived primary cancer cells.

cancer biology↗