Figure 5

Bulk RNA sequencing to comprehensively evaluate the effect of SMC)- EPC bi-level cell sheet transplantation on native tissue biological process following myocardial infarction. (A) Heart tissue was collected 7 days after surgery and the left ventricle was dissected into three zones encompassing the infarct, infarct border zone, and unaffected (remote). (B) Principal component analysis of the individual samples highlighted variable signatures in the anterior LV (infarct) and border zone regions between the cell sheet and untreated myocardial infarction models. (C) We identified 114 significantly enriched processes in cell sheet-treated hearts, including multiple pathways related to primitive morphogenesis, biological adhesion, and vasculature development. (D, E) Infarct samples showed significant enrichment for pathways related to mitochondrial energetics, oxidative phosphorylation, and protein translation. (F) Within the adhesion pathway, we found increased expression of critical ECM components following cell sheet treatment, including several collagen VI isoforms and multiple collagen subtypes associated with cardiac development and response to injury (Col12a1 and Col1a1). Each of these genes had low expression in sham samples and the remote, non-infarcted LV but showed enhanced expression following infarction, which was further enriched in cell sheet-treated samples, suggesting amplification of native ECM remodeling processes. (G) Within the vasculature development pathway, we observed heightened expression of Ndnf and Adam12, genes with known roles in angiogenic processes following cell sheet transplantation. Boxes denote interquartile range (IQR), the line represents the median, whiskers extend 1.5 IQR from box hinges.