Abstract 517: Transplantation of Mesenchymal Stem Cells Improves Atrioventricular Conduction in a Rat Model of Complete Atrioventricular Block
Background: Mesenchymal stem cells (MSCs) are multipotent cells that differentiate into a variety of lineages including myocytes and vascular endothelial cells. However, little information is available regarding the therapeutic potential of MSCs in patients with atrioventricular (AV) block. We investigated whether local implantation of MSCs improves AV conduction in a rat model of complete AV block.
Methods: Persistent complete AV block was achieved by injection of ethanol into the AV nodal region. To detect the site of AV block, His-bundle electrograms were recorded. Five days after ethanol injection, MSCs (MSC group) or vehicle (Control group) were injected into the AV nodal region. Animals were monitored by electrocardiogram for 14 days. Then, the heart was excised and histological examination was performed including Masson’s trichrome staining and the expression of transforming growth factor-β1 (TGF-β1). Immunofluorescent staining was performed with anti-neurofilament160 (NF160) as a marker of the conduction system, and anti-connexin-45 (Cx45) as a marker for gap junction.
Results: Rats with complete AV block showed atrial-to-His block. The AV conduction was recovered in five of 15 rats (33%) in the MSC group, accompanied with the improvement of electrophysi-ological parameters such as heart rate and ventricular cycle length, whereas no improvement was observed in the Control group even after 14 days. Compared with the Control group, MSC transplantation significantly decreased collagen deposition in the AV node, which was associated with a marked decrease in TGF-β1 expression. MSCs secreted a large amount of anti-fibrotic factors such as hepatocyte growth factor and interleukin-10. Furthermore, a small fraction of the transplanted MSCs were engrafted in the AV node, and some of them were positive for NF160 or Cx45 at contact points with native myocytes, suggesting that a fraction of transplanted MSCs regenerated functional myocytes.
Conclusions: MSC transplantation improved AV conduction in a rat model of complete AV block, possibly through inhibition of fibrosis as well as regeneration of functional AV nodal myocytes. MSC transplantation may be a new therapeutic strategy for the treatment of AV block.