Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs

Young Koh Gou Young Koh, Mark Soonpaa, M. G. Klug, H. P. Pride, B. J. Cooper, D. P. Zipes, Loren Field

Research output: Contribution to journalArticle

162 Citations (Scopus)

Abstract

This report documents the formation of stable fetal cardiomyocyte grafts in the myocardium of dystrophic dogs. Preliminary experiments established that the dystrophin gene product could be used to follow the fate of engrafted cardiomyocytes in dystrophic mdx mice. Importantly, ultrastructural analyses revealed the presence of intercalated discs consisting of fascia adherens, desmosomes, and gap junctions at the donor-host cardiomyocyte border. To determine if isolated cardiomyocytes could form stable intracardiac grafts in a larger species, preparations of dissociated fetal canine cardiomyocytes were delivered into the hearts of adult CX MD (canine X-linked muscular dystrophy) dogs. CXMD dugs, like Duchenne muscular dystrophy patients and mdx mice, fail to express dystrophin in both cardiac and skeletal muscle. Engrafted fetal cardiomyocytes, identified by virtue of dystrophin immunoreactivity, were observed to be tightly juxtaposed with host cardiomyocytes as long as 10 wk after engraftment, the latest date analyzed. Confocal laser scanning microscopy revealed the presence of connexin43, a major constituent of the gap junction, at the donor-host cardiomyocyte border. The presence of intracardiac grafts was not associated with arrhythmogenesis in the CXMD model. These results indicate that fetal cardiomyocyte grafting can successfully augment cardiomyocyte number in larger animals.

Original languageEnglish
Pages (from-to)2034-2042
Number of pages9
JournalJournal of Clinical Investigation
Volume96
Issue number4
StatePublished - 1995

Fingerprint

Cardiac Myocytes
Dogs
Transplants
Dystrophin
Inbred mdx Mouse
Gap Junctions
Canidae
Myocardium
Tissue Donors
Adherens Junctions
Desmosomes
Connexin 43
Muscular Dystrophies
Fascia
Confocal Microscopy
Skeletal Muscle

Keywords

  • cardiomyopathy
  • gene therapy
  • muscular dystrophy
  • myocardial repair

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Gou Young Koh, Y. K., Soonpaa, M., Klug, M. G., Pride, H. P., Cooper, B. J., Zipes, D. P., & Field, L. (1995). Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. Journal of Clinical Investigation, 96(4), 2034-2042.

Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. / Gou Young Koh, Young Koh; Soonpaa, Mark; Klug, M. G.; Pride, H. P.; Cooper, B. J.; Zipes, D. P.; Field, Loren.

In: Journal of Clinical Investigation, Vol. 96, No. 4, 1995, p. 2034-2042.

Research output: Contribution to journalArticle

Gou Young Koh, YK, Soonpaa, M, Klug, MG, Pride, HP, Cooper, BJ, Zipes, DP & Field, L 1995, 'Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs', Journal of Clinical Investigation, vol. 96, no. 4, pp. 2034-2042.
Gou Young Koh YK, Soonpaa M, Klug MG, Pride HP, Cooper BJ, Zipes DP et al. Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. Journal of Clinical Investigation. 1995;96(4):2034-2042.
Gou Young Koh, Young Koh ; Soonpaa, Mark ; Klug, M. G. ; Pride, H. P. ; Cooper, B. J. ; Zipes, D. P. ; Field, Loren. / Stable fetal cardiomyocyte grafts in the hearts of dystrophic mice and dogs. In: Journal of Clinical Investigation. 1995 ; Vol. 96, No. 4. pp. 2034-2042.
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