Journal
CELL TRANSPLANTATION
Volume 17, Issue 10-11, Pages 1145-1155Publisher
SAGE PUBLICATIONS INC
DOI: 10.3727/096368908787236594
Keywords
Atrioventricular node; Fibrosis; Atrioventricular block; Mesenchymal stem cell; Transplantation
Funding
- Ministry of Health, Labor and Welfare
- Program for Promotion of Fundamental Studies in Health Science of the National Institute of Biomedical Innovation (NIBIO)
- Ministry of Education, Culture, Sports, Science and Technology of Japan
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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 block (AVB). We investigated whether local implantation of MSCs improves AV conduction in a rat model of complete AVB. Complete AVB was achieved by injection of ethanol into the AV nodal region of Lewis rats. Five days after ethanol injection, 2 x 10(6) of MSCs (MSC group) or vehicle (Control group) were injected into the AV nodal region. Animals were monitored by electrocardiograms for 14 days, and physiological and histological examinations were performed. The 1:1 AV conduction was recovered in 5 of 15 rats (33670) in the MSC group during the follow-up period, whereas no improvement was observed in the control group. MSC transplantation significantly decreased collagen deposition in the AV node, which was associated with a marked decrease in transforming growth factor-beta 1 expression. In vitro experiments demonstrated that MSCs secreted a large amount of antifibrotic factors such as hepatocyte growth factor and interleukin-10, and MSC conditioned medium inhibited the growth of adult cardiac fibroblasts. In addition, local injection of MSC conditioned medium recovered AV conduction in 2 of 15 rats (13670). MSC transplantation improved AV conduction in a rat model of complete AVB, at least in part through antifibrotic paracrine effects.
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