Abstract 2973: Development of the Targeting for Myocardium by Artificial Glycoside-coated Bone Marrow Cells
Background: Recently, bone marrow cell implantation (BMI) has been performed to treat ischemic heart disease. To enhance the effects of BMI, it is important to increase an accumulation of bone marrow cells (BMCs) in the infarcted myocardium. Previously, we reported that cardiomyocytes strongly interact with N-acethylglucosamine (GlcNAc) and take up GlcNAc-conjugated liposomes. Here, we examined whether artificial GlcNAc-coated BMCs could promote their interaction with the myocardium.
Methods and Results: We tested whether GlcNAc could be coated to the cell surface of BMCs by GlcNAc-lipophilic polymers. BMCs were incubated with 25 μg/mL GlcNAc-lipophilic polymers for 30 min at 4°C. Flow cytometric analysis showed that the surface of BMCs was coated with GlcNAc without any cellular damage. In coculture of the GlcNAc-coated BMCs with cardiomyocytes, these BMCs showed high interaction with cardiomyocytes and the number of the BMCs that attached to cardiomyocytes was 5-fold higher than that of uncoated BMCs. After cardiomyocytes were cocultured with GlcNAc-coated BMCs isolated from green fluorescence protein (GFP) transgenic rats for 7 days, BMC-derived cardiomyocytes (GFP+/actinin+ or desmin+ cells) were detected. The frequency of the BMC-derived cardiomyocytes was 4-fold higher in coculture of GlcNAc-coated BMCs than that in coculture of uncoated BMCs, suggesting that these BMC-derived cardiomyocytes may come from cell fusion between BMCs and cardiomyocytes. The fusion of BMCs with cardiomyocytes was promoted by high interaction of GlcNAc-coated BMCs with cardiomyocytes. Furthermore, we performed the BMI to the ischemia-reperfused heart of mice by intravenous injection. At 2 days after BMI, the number of the GlcNAc-coated BMCs accumulated in the reperfused myocardium was significantly higher than that of the uncoated BMCs (p<0.05).
Conclusions: The surface of BMCs was coated with GlcNAc by GlcNAc-lipophilic polymers. Furthermore, GlcNAc-coated BMCs showed high interaction with cardiomyocytes and this interaction promoted the fusion between BMCs and cardiomyocytes. This study suggests that the coating of GlcNAc to the surface of BMCs could improve the therapeutic effect of BMI for ischemic cardiovascular diseases.