Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle

Theo Kofidis, Jorg L. De Bruin, Grant Hoyt, Darren R. Lebl, Masashi Tanaka, Toshiyuki Yamane, Ching-Pin Chang, Robert C. Robbins

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Most tissue-engineering approaches to restore injured heart muscle result in distortion of left ventricular geometry. In the present study we suggest seeding embryonic stem cells in a liquid matrix for myocardial restoration. Undifferentiated green fluorescent protein-labeled mouse embryonic stem cells (2 × 10 6) were seeded in Matrigel (B&D, Bedford, Mass). In a Lewis rat heterotopic heart transplant model an intramural left ventricular pouch was fashioned after ligation of the left anterior descending coronary artery. The liquid mixture (0.125 mL) was injected in the resulting infarcted area within the pouch and solidified within a few minutes after transplantation (37°C). Five recipient groups were formed: transplanted healthy hearts (group I), infarcted control hearts (group II), matrix recipients alone (group III), the study group that received matrix plus cells (group IV), and a group that received embryonic stem cells alone (group V). After echocardiography 2 weeks later, the hearts were harvested and stained for green fluorescent protein and cardiac muscle markers (connexin 43 and α-sarcomeric actin). The graft formed a sustained structure within the injured area and prevented ventricular wall thinning. The inoculated cells remained viable and expressed connexin 43 and α-sarcomeric actin. Fractional shortening and regional contractility were better in animals that received bioartificial tissue grafts compared with control animals (infarcted, matrix only, and embryonic stem cells only: group I, 17.0% ± 3.5%; group II, 6.6% ± 2.1%; group III, 10.3% ± 2.2%; group IV, 14.5% ± 2.5%; and group V, 7.8% ± 1.8%). Liquid bioartificial tissue containing embryonic stem cells constitutes a powerful new approach to restoring injured heart muscle without distorting its geometry and structure.

Original languageEnglish (US)
Pages (from-to)571-578
Number of pages8
JournalJournal of Thoracic and Cardiovascular Surgery
Volume128
Issue number4
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Embryonic Stem Cells
Myocardium
Injections
Connexin 43
Green Fluorescent Proteins
Transplants
Actins
Tissue Engineering
Ligation
Echocardiography
Coronary Vessels
Transplantation

Keywords

  • 18,29,30

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery

Cite this

Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. / Kofidis, Theo; De Bruin, Jorg L.; Hoyt, Grant; Lebl, Darren R.; Tanaka, Masashi; Yamane, Toshiyuki; Chang, Ching-Pin; Robbins, Robert C.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 128, No. 4, 10.2004, p. 571-578.

Research output: Contribution to journalArticle

Kofidis, Theo ; De Bruin, Jorg L. ; Hoyt, Grant ; Lebl, Darren R. ; Tanaka, Masashi ; Yamane, Toshiyuki ; Chang, Ching-Pin ; Robbins, Robert C. / Injectable bioartificial myocardial tissue for large-scale intramural cell transfer and functional recovery of injured heart muscle. In: Journal of Thoracic and Cardiovascular Surgery. 2004 ; Vol. 128, No. 4. pp. 571-578.
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