Intrapericardial Administration of Human Pericardial Fluid Cells Improves Cardiac Functions in Rats with Heart Failure

Heart failure is still the main cause of mortality worldwide. This study investigated the characteristics of human pericardial fluid-derived cells (hPFCs) and their effects in treating doxorubicin (DOX)-induced heart failure (HF) rats through intrapericardial injection. hPFCs were isolated from patients who underwent heart transplantation (N=5). These cells that primarily expressed SCA-1, NANOG, mesenchymal markers CD90, CD105 and CD73, were able to form adipocytes, osteoblasts, and cardiomyocytes in vitro. Passage 3 hPFCs (2.5 ×105 cells/heart) were injected into the pericardial cavity of the doxorubicin (DOX)-injured rat hearts, significantly improving cardiac functions after 4 weeks. The tracked and engrafted RFP-tagged hPFCs co-expressed cardiac troponin T and connexin 43 after 4 weeks in the host myocardium. This observation was also coupled with a significant reduction in cardiac fibrosis following hPFCs treatment (P<0.0001 versus untreated). The elevated inflammatory cytokine IL-6, IL-10, and TNF-α in the DOX-treated hearts were found to have significantly reduced (P<0.001 versus untreated), while the regional pro-angiogenic vascular endothelial growth factor A (VEGFA) level was increased in the hPFCs-treated group after 4 weeks (P<0.05 versus untreated). hPFCs possess stem cell characteristics and can improve cardiac functions of DOX-induced heart failure rats after 4 weeks through pericardial administration. The improvements were attributed to a significant reduction in cardiac fibrosis, inflammation, and elevated regional pro-angiogenesis factor VEGFA, with evidence of cellular engraftment and differentiation in the host myocardium.