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

Sook Kyoung Kim, Hui Nam Pak, Gwang Il Kim, Jae Hyung Park, Yong Fu Fang, Hong Euy Lim, Byung Soo Kim, Chun Hwang, Young Hoon Kim

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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.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalKorean Circulation Journal
Issue number10
Publication statusPublished - 2008 Oct 1


All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

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