Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart

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

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Although electrical pacing is of great utility in many cardiovascular diseases, its effects on the combined cardiac cell therapy have not been established. We hypothesised that mesenchymal stem cell transplantation changes cardiac sympathetic nerve and gap junction, and concomitant pacing has additional biological effects.Methods We monitored cardiac rhythm for 4 weeks after human mesenchymal stem cell transplantation (1 107, epicardial injection) in 18 dogs in vivo, seven human mesenchymal stem cell with pacing, six human mesenchymal stem cell, and five sham, and evaluated the sympathetic innervation, nerve growth factor-; tyrosine hydroxylase, angiogenesis, von Willebrand factor, and connexin43 expressions by real time (RT)-polymerase chain reaction and immunostaining. We also measured mRNA expressions of nerve growth factor-, von Willebrand factor, and connexin43 in vitro culture of human mesenchymal stem cell with or without pacing.Results Human mesenchymal stem cell transplanted hearts expressed higher mRNA of nerve growth factor- (p < 0.01) with sympathetic nerves (p < 0.05), higher mRNA of von Willebrand factor (p < 0.001) with angiogenesis (p < 0.001), but lower mRNA of connexin43 (p < 0.0001) with reduced gap junctions (p < 0.001) than sham. Pacing with human mesenchymal stem cell transplantation resulted in higher expression of mRNA of connexin43 (p < 0.02) and gap junctions (p < 0.001) compared with sham. In contrast, in vitro paced mesenchymal stem cell reduced expression of connexin43 mRNA (p < 0.02).Conclusion Human mesenchymal stem cell transplantation increased cardiac sympathetic innervation and angiogenesis, but reduced gap junction after transplanted in the canine heart. In contrast, concomitant electrical pacing increased gap junction expression by paracrine action.

Original languageEnglish
Pages (from-to)308-317
Number of pages10
JournalCardiology in the Young
Volume20
Issue number3
DOIs
Publication statusPublished - 2010 Apr 1

Fingerprint

Connexin 43
Gap Junctions
Cell- and Tissue-Based Therapy
Mesenchymal Stromal Cells
Canidae
Mesenchymal Stem Cell Transplantation
Messenger RNA
von Willebrand Factor
Nerve Growth Factor
Tyrosine 3-Monooxygenase
Real-Time Polymerase Chain Reaction
Cardiovascular Diseases
Dogs
Injections

Keywords

  • Gap junction
  • Nerve growth factor
  • Sympathetic nerve

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pediatrics, Perinatology, and Child Health

Cite this

@article{dfcb5ccd76c3460e86d3819c911e6d3e,
title = "Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart",
abstract = "Background: Although electrical pacing is of great utility in many cardiovascular diseases, its effects on the combined cardiac cell therapy have not been established. We hypothesised that mesenchymal stem cell transplantation changes cardiac sympathetic nerve and gap junction, and concomitant pacing has additional biological effects.Methods We monitored cardiac rhythm for 4 weeks after human mesenchymal stem cell transplantation (1 107, epicardial injection) in 18 dogs in vivo, seven human mesenchymal stem cell with pacing, six human mesenchymal stem cell, and five sham, and evaluated the sympathetic innervation, nerve growth factor-; tyrosine hydroxylase, angiogenesis, von Willebrand factor, and connexin43 expressions by real time (RT)-polymerase chain reaction and immunostaining. We also measured mRNA expressions of nerve growth factor-, von Willebrand factor, and connexin43 in vitro culture of human mesenchymal stem cell with or without pacing.Results Human mesenchymal stem cell transplanted hearts expressed higher mRNA of nerve growth factor- (p < 0.01) with sympathetic nerves (p < 0.05), higher mRNA of von Willebrand factor (p < 0.001) with angiogenesis (p < 0.001), but lower mRNA of connexin43 (p < 0.0001) with reduced gap junctions (p < 0.001) than sham. Pacing with human mesenchymal stem cell transplantation resulted in higher expression of mRNA of connexin43 (p < 0.02) and gap junctions (p < 0.001) compared with sham. In contrast, in vitro paced mesenchymal stem cell reduced expression of connexin43 mRNA (p < 0.02).Conclusion Human mesenchymal stem cell transplantation increased cardiac sympathetic innervation and angiogenesis, but reduced gap junction after transplanted in the canine heart. In contrast, concomitant electrical pacing increased gap junction expression by paracrine action.",
keywords = "Gap junction, Nerve growth factor, Sympathetic nerve",
author = "Kim, {Sook Kyoung} and Pak, {Hui Nam} and Park, {Jae Hyung} and Fang, {Yong Fu} and Kim, {Gwang Il} and Yongdoo Park and Chun Hwang and Kim, {Young Hoon} and Kim, {Byung Soo}",
year = "2010",
month = "4",
day = "1",
doi = "10.1017/S1047951110000132",
language = "English",
volume = "20",
pages = "308--317",
journal = "Cardiology in the Young",
issn = "1047-9511",
publisher = "Cambridge University Press",
number = "3",

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TY - JOUR

T1 - Cardiac cell therapy with mesenchymal stem cell induces cardiac nerve sprouting, angiogenesis, and reduced connexin43-positive gap junctions, but concomitant electrical pacing increases connexin43-positive gap junctions in canine heart

AU - Kim, Sook Kyoung

AU - Pak, Hui Nam

AU - Park, Jae Hyung

AU - Fang, Yong Fu

AU - Kim, Gwang Il

AU - Park, Yongdoo

AU - Hwang, Chun

AU - Kim, Young Hoon

AU - Kim, Byung Soo

PY - 2010/4/1

Y1 - 2010/4/1

N2 - Background: Although electrical pacing is of great utility in many cardiovascular diseases, its effects on the combined cardiac cell therapy have not been established. We hypothesised that mesenchymal stem cell transplantation changes cardiac sympathetic nerve and gap junction, and concomitant pacing has additional biological effects.Methods We monitored cardiac rhythm for 4 weeks after human mesenchymal stem cell transplantation (1 107, epicardial injection) in 18 dogs in vivo, seven human mesenchymal stem cell with pacing, six human mesenchymal stem cell, and five sham, and evaluated the sympathetic innervation, nerve growth factor-; tyrosine hydroxylase, angiogenesis, von Willebrand factor, and connexin43 expressions by real time (RT)-polymerase chain reaction and immunostaining. We also measured mRNA expressions of nerve growth factor-, von Willebrand factor, and connexin43 in vitro culture of human mesenchymal stem cell with or without pacing.Results Human mesenchymal stem cell transplanted hearts expressed higher mRNA of nerve growth factor- (p < 0.01) with sympathetic nerves (p < 0.05), higher mRNA of von Willebrand factor (p < 0.001) with angiogenesis (p < 0.001), but lower mRNA of connexin43 (p < 0.0001) with reduced gap junctions (p < 0.001) than sham. Pacing with human mesenchymal stem cell transplantation resulted in higher expression of mRNA of connexin43 (p < 0.02) and gap junctions (p < 0.001) compared with sham. In contrast, in vitro paced mesenchymal stem cell reduced expression of connexin43 mRNA (p < 0.02).Conclusion Human mesenchymal stem cell transplantation increased cardiac sympathetic innervation and angiogenesis, but reduced gap junction after transplanted in the canine heart. In contrast, concomitant electrical pacing increased gap junction expression by paracrine action.

AB - Background: Although electrical pacing is of great utility in many cardiovascular diseases, its effects on the combined cardiac cell therapy have not been established. We hypothesised that mesenchymal stem cell transplantation changes cardiac sympathetic nerve and gap junction, and concomitant pacing has additional biological effects.Methods We monitored cardiac rhythm for 4 weeks after human mesenchymal stem cell transplantation (1 107, epicardial injection) in 18 dogs in vivo, seven human mesenchymal stem cell with pacing, six human mesenchymal stem cell, and five sham, and evaluated the sympathetic innervation, nerve growth factor-; tyrosine hydroxylase, angiogenesis, von Willebrand factor, and connexin43 expressions by real time (RT)-polymerase chain reaction and immunostaining. We also measured mRNA expressions of nerve growth factor-, von Willebrand factor, and connexin43 in vitro culture of human mesenchymal stem cell with or without pacing.Results Human mesenchymal stem cell transplanted hearts expressed higher mRNA of nerve growth factor- (p < 0.01) with sympathetic nerves (p < 0.05), higher mRNA of von Willebrand factor (p < 0.001) with angiogenesis (p < 0.001), but lower mRNA of connexin43 (p < 0.0001) with reduced gap junctions (p < 0.001) than sham. Pacing with human mesenchymal stem cell transplantation resulted in higher expression of mRNA of connexin43 (p < 0.02) and gap junctions (p < 0.001) compared with sham. In contrast, in vitro paced mesenchymal stem cell reduced expression of connexin43 mRNA (p < 0.02).Conclusion Human mesenchymal stem cell transplantation increased cardiac sympathetic innervation and angiogenesis, but reduced gap junction after transplanted in the canine heart. In contrast, concomitant electrical pacing increased gap junction expression by paracrine action.

KW - Gap junction

KW - Nerve growth factor

KW - Sympathetic nerve

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U2 - 10.1017/S1047951110000132

DO - 10.1017/S1047951110000132

M3 - Article

VL - 20

SP - 308

EP - 317

JO - Cardiology in the Young

JF - Cardiology in the Young

SN - 1047-9511

IS - 3

ER -