Abstract 944: TNF-α Enhances the Engraftment of Mesenchymal Stem Cells onto Infarcted Myocardium via BMP-2
Background: Mesenchymal stem cells (MSCs) have therapeutic potential after myocardial infarction. We hypothesized that cytokines released from infarcted myocardium play an important role in recruit and potentiation of MSCs. We elucidated whether TNF-α, one of cytokine released from infarcted myocardium, modulate the behavior of rat bone marrow-MSCs in vivo and in vitro system.
Methods: Allogeneic MSCs were isolated from the femoral bone of Sprague-Dawley rats, characterized, cultured, and labeled with DAPI. To examine the effect of TNF-α on MSC, MSCs were treated with TNF-α (10 ng/mL) for 24 hours before injected into infarcted myocardium of rats. Myocardial infarction was induced by left anterior descending coronary artery ligation for 30 minutes followed by release. Two weeks later, the number of DAPI-labelled MSCs on myocardium of rat was counted. To measure the adhesiveness of MSC, neonatal rat cardiomyocytes were co-cultured with DAPI-labeled MSC with or without TNF-α pretreatment. After 30 minutes, non-adhesive MSCs were removed, and remained MSCs on cardiomyocytes were counted under fluorescent microscope.
Results: The expression of BMP-2 was increased by TNF-α in mRNA (2.7-fold of control, p<0.05) and protein level (3.23±0.43 ng/mL in MSC vs. 5.81±0.75 ng/mL in TNF-α-treated MSC, p<0.05). The expressions of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, vascular endothelial growth factor (VEGF), and phosphorylated signal transducer and activator of transcription (STAT)-3 were also increased in TNF-α treated MSCs. The number of engrafted TNF-α-stimulated MSCs on rat myocardium was larger than non-treated MSCs (1.82-fold, p<0.05). Adhesion assay showed that the adhesiveness of TNF-α-stimulated MSCs on cardiomyocytes was 1.74-fold increased (p<0.05).
Conclusion: Our results demonstrated that TNF-α improved the engraftment of MSCs on infarcted myocardium through increase its adhesiveness and BMP-2 probably acted as a putative mediator.