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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)536-543
Number of pages8
JournalKorean Circulation Journal
Volume38
Issue number10
DOIs
Publication statusPublished - 2008 Oct 1

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Mesenchymal Stem Cell Transplantation
Gap Junctions
Dogs
Mesenchymal Stromal Cells
Connexin 43
Nerve Growth Factor
Tyrosine 3-Monooxygenase
Ventricular Fibrillation
RNA
Injections
Ventricular Function

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Kim, Sook Kyoung ; pak, huinam ; Kim, Gwang Il ; Park, Jae Hyung ; Fang, Yong Fu ; Lim, Hong Euy ; Kim, Byung Soo ; Hwang, Chun ; Kim, Young Hoon. / Human mesenchymal stem cell transplantation induces sympathetic nerve sprouting and reduces the gap junction with potential proarrhythmias in dogs. In: Korean Circulation Journal. 2008 ; Vol. 38, No. 10. pp. 536-543.
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title = "Human mesenchymal stem cell transplantation induces sympathetic nerve sprouting and reduces the gap junction with potential proarrhythmias in dogs",
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.",
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Human mesenchymal stem cell transplantation induces sympathetic nerve sprouting and reduces the gap junction with potential proarrhythmias in dogs. / Kim, Sook Kyoung; pak, huinam; Kim, Gwang Il; Park, Jae Hyung; Fang, Yong Fu; Lim, Hong Euy; Kim, Byung Soo; Hwang, Chun; Kim, Young Hoon.

In: Korean Circulation Journal, Vol. 38, No. 10, 01.10.2008, p. 536-543.

Research output: Contribution to journalArticle

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T1 - Human mesenchymal stem cell transplantation induces sympathetic nerve sprouting and reduces the gap junction with potential proarrhythmias in dogs

AU - Kim, Sook Kyoung

AU - pak, huinam

AU - Kim, Gwang Il

AU - Park, Jae Hyung

AU - Fang, Yong Fu

AU - Lim, Hong Euy

AU - Kim, Byung Soo

AU - Hwang, Chun

AU - Kim, Young Hoon

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N2 - 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.

AB - 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.

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