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KMID : 0368120080380100536
Korean Circulation Journal
2008 Volume.38 No. 10 p.536 ~ p.543
Human Mesenchymal Stem Cell Transplantation Induces Sympathetic Nerve Sprouting and Reduces the Gap Junction With Potential Proarrhythmias in Dogs
Kim Sook-Kyoung

Pak Hui-Nam
Kim Kwang-Il
Park Jae-Hyung
Fang Yong-Fu
Lim Hong-Euy
Kim Byung-Soo
Kim Young-Hoon
Abstract
Background and Objectives: Although human mesenchymal stem cell (hMSC) transplantation has been known to improve ventricular function, the potential proarrhythmic effects have not yet been studied.

Materials and Methods: We monitored the heart rhythm of 6 dogs for 4 weeks after transplantation of hMSC (1¡¿107, epicardial injection) (hMSC group) and in 5 Sham dogs after the injection of the vehicle alone. Cardiac sympathetic nerve sprouting {nerve growth factor (NGF)-¥â; tyrosine hydroxylase (TH)} and gap junction expression {connexin (Cx) 43} were evaluated in 10 dogs (5 hMSC and 5 Sham) that survived longer than 4 weeks.

Results: The hMSC group expressed higher levels of NGF-¥â messenger ribonucleic acid (mRNA) (56.0¡¾66.8 fold; p<0.01) with TH+ sympathetic nerves (0.51¡¾0.40 vs. 0.15¡¾0.13% area; p<0.03) than the Sham control. In contrast, the hMSC group expressed lower levels of Cx43 mRNA (0.59¡¾0.29 fold, p<0.001) and Cx43+ (1.64¡¾1.79 vs. 2.12¡¾1.07% area, p<0.001) than the Sham control. The incidences of ventricular fibrillation were 33.3% and 0% in the hMSC group and Sham control, respectively. One of the dogs with ventricular fibrillation (VF) in the hMSC group died suddenly.

Conclusion: hMSC transplantation may be proarrhythmic since NGF-¥â expression increased with cardiac sympathetic hyperinnervation and the expression of Cx43 and the gap junction decreased.
KEYWORD
Mesenchymal stem cells, Nerve growth factor, Gap Junctions, Ventricular tachycardia
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