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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

Published online by Cambridge University Press:  29 March 2010

Sook Kyoung Kim ,
Hui-Nam Pak ,
Jae Hyung Park ,
Yong Fu Fang ,
Gwang Il Kim ,
Yong Doo Park ,
Chun Hwang ,
Young-Hoon Kim  and
Byung Soo Kim
Sook Kyoung Kim
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Hui-Nam Pak*
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Jae Hyung Park
Affiliation:
Department of Cardiology, Yonsei University Health System, Seoul, Korea
Yong Fu Fang
Affiliation:
Department of Cardiology, Korea University Cardiovascular Center, Seoul, Korea
Gwang Il Kim
Affiliation:
Department of Pathology, College of Medicine, Pochon CHA University, Seoul, Korea
Yong Doo Park
Affiliation:
Department of Biomedical Engineering, Korea University, Seoul, Korea
Chun Hwang
Affiliation:
Utah Valley Medical Center, Provo, UT, United States of America
Young-Hoon Kim
Affiliation:
Department of Cardiology, Korea University Cardiovascular Center, Seoul, Korea
Byung Soo Kim
Affiliation:
Department of Hematology, Korea University, Seoul, Korea
*
Correspondence to: H.-N. Pak, MD, PhD, 250 Seungsanno, Seodaemu, Seoul, Republic of Korea 120-752. Tel: +82 2 –2228 58459; Fax: +82 2 393 2041; E-mail: hnpak@yuhs.ac
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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-β; 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-β, 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-β (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

Sympathetic nervenerve growth factorgap junction
Type
Original Articles
Information
Cardiology in the Young , Volume 20 , Issue 3 , June 2010 , pp. 308 - 317
Copyright
Copyright © Cambridge University Press 2010

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