Homing of adipose-derived stem cells to radiofrequency catheter ablated canine atrium and differentiation into cardiomyocyte-like cells

Abstract

Background and objectives: The purpose was to determine whether human adipose-derived stem cells (h-ASCs) can home to the radiofrequency ablated myocardial lesions when injected intravenously and differentiate into cardiomyocyte.

Methods: Human adipose tissues were obtained from patients and h-ASCs were isolated and cultured. The phenotype of isolated h-ASCs was identified by flow cytometry. Radiofrequency catheter ablation (RFCA) was performed with ten ablation pulses (40 W, 60 s each) to induce heat-mediated lesions at the free walls of the right atria of 14 dogs. Twenty-four hours after ablation, h-ASCs (1 × 10(7) cells) labeled with superparamagnetic iron oxide particles (SPIOs) were infused intravenously in 10 dogs as cell-therapy group and only saline without cells was infused in 4 dogs as control. The hearts were explanted 4 weeks later.

Results: h-ASCs were identified by flow cytometry as mesenchymal stem cell as positive for CD 13, CD29, CD44, CD90, CD166 and HLA-ABC and immunophenotyping revealed no immunologic responses. SPIO-labeled cells were identified in areas surrounding the RFCA-induced lesions by Prussian blue staining. Immunohistochemistry staining showed positive for anti-α-actinin, anti-cardiac troponin-I, anti-connexin 43 and anti-VEGFR-2. No lymphocyte infiltration, immunorejection or neoplasm-like cells were found in the h-ASC-positive areas. However, multiple iron-labeled h-ASCs were detected in lungs and spleens of cell-therapy group.

Conclusion: h-ASCs can home into injured atrial tissue and express a cardiomyocyte-like phenotype, suggesting that intravenous delivery of stem cells might be feasible. Functional studies and quantification of delivered stem cells are needed for better evaluation and understanding of differentiation into cardiomyocytes.