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Human mesenchymal stem cell transplantation induces sympathetic nerve sprouting and reduces the gap junction with potential proarrhythmias in dogs

Authors
Kim, S.K.Pak, H.-N.Kim, G.I.Park, J.H.Fang, Y.F.Lim, H.E.Kim, B.S.Hwang, C.Kim, Y.-H.
Issue Date
2008
Keywords
Gap Junctions; Mesenchymal stem cells; Nerve growth factor; Ventricular tachycardia
Citation
Korean Circulation Journal, v.38, no.10, pp.536 - 543
Indexed
SCOPUS
KCI
Journal Title
Korean Circulation Journal
Volume
38
Number
10
Start Page
536
End Page
543
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/125360
DOI
10.4070/kcj.2008.38.10.536
ISSN
1738-5520
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)- β; 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- β messenger ribonucleic acid (mRNA) (56.0 ± 66.8 fold; p<0.01) with TH+ sympathetic nerves (0.51 ± 0.40 vs. 0.15 ± 0.13% area; p<0.03) than the Sham control. In contrast, the hMSC group expressed lower levels of Cx43 mRNA (0,59 ± 0.29 fold, p<0.001) and Cx43+ (1.64 ± 1.79 vs. 2.12 ± 1.07% 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- β expression increased with cardiac sympathetic hyperinnervation and the expression of Cx43 and the gap junction decreased. Copyright © 2008 The Korean Society of Cardiology.
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