Myocardial restoration with embryonic stem cell bioartificial tissue transplantation

Theo Kofidis, Jorg L. De Bruin, Grant Hoyt, Yen Ho, Masashi Tanaka, Toshiyuki Yamane, Darren R. Lebl, Rutger Jan Swijnenburg, Ching-Pin Chang, Thomas Quertermous, Robert C. Robbins

Research output: Contribution to journalArticle

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Abstract

Background: The optimal cell-matrix combination for robust and sustained myocardial restoration has not been identified. The present study utilizes embryonic stem cells as the substrate of bioartificial myocardial tissue and evaluates engraftment in, and functional recovery of, the recipient heart. Methods: Collagen type I was populated with undifferentiated green fluorescent protein (GFP)-positive mouse embryonic stem cells. An intramural left ventricular pouch was fashioned after ligation of the left anterior descending artery in an athymic nude rat heterotopic heart transplant model. The bioartificial mixture (0.125 ml) was implanted in the infarcted area within the pouch. Echocardiography was performed to assess fractional shortening in: Group I, infarcted rats that received cell-matrix implants; Group II, rats given matrix implant without cells; Group III, rats given no matrix or cells; and Group IV, rats receiving transplanted hearts without ligation (n = 5/group). Hearts were stained for GFP, cardiac markers (connexin-43, α-sarcomeric actin), hematoxylin-eosin (H&E) and trichrome. Results: Embryonic stem cells formed stable intramyocardial grafts that were incorporated into the surrounding area without distorting myocardial geometry, thereby preventing ventricular wall thinning (anterior wall thickness was: Group I, 1.4 ± 0.1 mm; Group II, 1.0 ± 0.1 mm, Group III, 0.9 ± 0.2 mm; and Group IV, 1.3 ± 0.2 mm). The inoculated cells expressed connexin-43 and α-sarcomeric actin in vivo. Fractional shortening was better in embryonic stem cell-treated animals (Group I, 21.5 ± 3.5%; Group II, 12.4 ± 2.8%; Group III, 8.2 ± 2.9%; Group IV, 23.2 ± 4.2%). Conclusions: Embryonic stem cells are an efficient alternative substrate for myocardial tissue engineering and can prevent myocardial wall thinning and improve contractility after implantation into injured myocardium in a 3-dimensional matrix.

Original languageEnglish (US)
Pages (from-to)737-744
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume24
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Tissue Transplantation
Embryonic Stem Cells
Nude Rats
Connexin 43
Green Fluorescent Proteins
Ligation
Actins
Transplants
Hematoxylin
Tissue Engineering
Eosine Yellowish-(YS)
Collagen Type I
Echocardiography
Myocardium
Arteries

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Kofidis, T., De Bruin, J. L., Hoyt, G., Ho, Y., Tanaka, M., Yamane, T., ... Robbins, R. C. (2005). Myocardial restoration with embryonic stem cell bioartificial tissue transplantation. Journal of Heart and Lung Transplantation, 24(6), 737-744. https://doi.org/10.1016/j.healun.2004.03.023

Myocardial restoration with embryonic stem cell bioartificial tissue transplantation. / Kofidis, Theo; De Bruin, Jorg L.; Hoyt, Grant; Ho, Yen; Tanaka, Masashi; Yamane, Toshiyuki; Lebl, Darren R.; Swijnenburg, Rutger Jan; Chang, Ching-Pin; Quertermous, Thomas; Robbins, Robert C.

In: Journal of Heart and Lung Transplantation, Vol. 24, No. 6, 06.2005, p. 737-744.

Research output: Contribution to journalArticle

Kofidis, T, De Bruin, JL, Hoyt, G, Ho, Y, Tanaka, M, Yamane, T, Lebl, DR, Swijnenburg, RJ, Chang, C-P, Quertermous, T & Robbins, RC 2005, 'Myocardial restoration with embryonic stem cell bioartificial tissue transplantation', Journal of Heart and Lung Transplantation, vol. 24, no. 6, pp. 737-744. https://doi.org/10.1016/j.healun.2004.03.023
Kofidis, Theo ; De Bruin, Jorg L. ; Hoyt, Grant ; Ho, Yen ; Tanaka, Masashi ; Yamane, Toshiyuki ; Lebl, Darren R. ; Swijnenburg, Rutger Jan ; Chang, Ching-Pin ; Quertermous, Thomas ; Robbins, Robert C. / Myocardial restoration with embryonic stem cell bioartificial tissue transplantation. In: Journal of Heart and Lung Transplantation. 2005 ; Vol. 24, No. 6. pp. 737-744.
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abstract = "Background: The optimal cell-matrix combination for robust and sustained myocardial restoration has not been identified. The present study utilizes embryonic stem cells as the substrate of bioartificial myocardial tissue and evaluates engraftment in, and functional recovery of, the recipient heart. Methods: Collagen type I was populated with undifferentiated green fluorescent protein (GFP)-positive mouse embryonic stem cells. An intramural left ventricular pouch was fashioned after ligation of the left anterior descending artery in an athymic nude rat heterotopic heart transplant model. The bioartificial mixture (0.125 ml) was implanted in the infarcted area within the pouch. Echocardiography was performed to assess fractional shortening in: Group I, infarcted rats that received cell-matrix implants; Group II, rats given matrix implant without cells; Group III, rats given no matrix or cells; and Group IV, rats receiving transplanted hearts without ligation (n = 5/group). Hearts were stained for GFP, cardiac markers (connexin-43, α-sarcomeric actin), hematoxylin-eosin (H&E) and trichrome. Results: Embryonic stem cells formed stable intramyocardial grafts that were incorporated into the surrounding area without distorting myocardial geometry, thereby preventing ventricular wall thinning (anterior wall thickness was: Group I, 1.4 ± 0.1 mm; Group II, 1.0 ± 0.1 mm, Group III, 0.9 ± 0.2 mm; and Group IV, 1.3 ± 0.2 mm). The inoculated cells expressed connexin-43 and α-sarcomeric actin in vivo. Fractional shortening was better in embryonic stem cell-treated animals (Group I, 21.5 ± 3.5{\%}; Group II, 12.4 ± 2.8{\%}; Group III, 8.2 ± 2.9{\%}; Group IV, 23.2 ± 4.2{\%}). Conclusions: Embryonic stem cells are an efficient alternative substrate for myocardial tissue engineering and can prevent myocardial wall thinning and improve contractility after implantation into injured myocardium in a 3-dimensional matrix.",
author = "Theo Kofidis and {De Bruin}, {Jorg L.} and Grant Hoyt and Yen Ho and Masashi Tanaka and Toshiyuki Yamane and Lebl, {Darren R.} and Swijnenburg, {Rutger Jan} and Ching-Pin Chang and Thomas Quertermous and Robbins, {Robert C.}",
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T1 - Myocardial restoration with embryonic stem cell bioartificial tissue transplantation

AU - Kofidis, Theo

AU - De Bruin, Jorg L.

AU - Hoyt, Grant

AU - Ho, Yen

AU - Tanaka, Masashi

AU - Yamane, Toshiyuki

AU - Lebl, Darren R.

AU - Swijnenburg, Rutger Jan

AU - Chang, Ching-Pin

AU - Quertermous, Thomas

AU - Robbins, Robert C.

PY - 2005/6

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N2 - Background: The optimal cell-matrix combination for robust and sustained myocardial restoration has not been identified. The present study utilizes embryonic stem cells as the substrate of bioartificial myocardial tissue and evaluates engraftment in, and functional recovery of, the recipient heart. Methods: Collagen type I was populated with undifferentiated green fluorescent protein (GFP)-positive mouse embryonic stem cells. An intramural left ventricular pouch was fashioned after ligation of the left anterior descending artery in an athymic nude rat heterotopic heart transplant model. The bioartificial mixture (0.125 ml) was implanted in the infarcted area within the pouch. Echocardiography was performed to assess fractional shortening in: Group I, infarcted rats that received cell-matrix implants; Group II, rats given matrix implant without cells; Group III, rats given no matrix or cells; and Group IV, rats receiving transplanted hearts without ligation (n = 5/group). Hearts were stained for GFP, cardiac markers (connexin-43, α-sarcomeric actin), hematoxylin-eosin (H&E) and trichrome. Results: Embryonic stem cells formed stable intramyocardial grafts that were incorporated into the surrounding area without distorting myocardial geometry, thereby preventing ventricular wall thinning (anterior wall thickness was: Group I, 1.4 ± 0.1 mm; Group II, 1.0 ± 0.1 mm, Group III, 0.9 ± 0.2 mm; and Group IV, 1.3 ± 0.2 mm). The inoculated cells expressed connexin-43 and α-sarcomeric actin in vivo. Fractional shortening was better in embryonic stem cell-treated animals (Group I, 21.5 ± 3.5%; Group II, 12.4 ± 2.8%; Group III, 8.2 ± 2.9%; Group IV, 23.2 ± 4.2%). Conclusions: Embryonic stem cells are an efficient alternative substrate for myocardial tissue engineering and can prevent myocardial wall thinning and improve contractility after implantation into injured myocardium in a 3-dimensional matrix.

AB - Background: The optimal cell-matrix combination for robust and sustained myocardial restoration has not been identified. The present study utilizes embryonic stem cells as the substrate of bioartificial myocardial tissue and evaluates engraftment in, and functional recovery of, the recipient heart. Methods: Collagen type I was populated with undifferentiated green fluorescent protein (GFP)-positive mouse embryonic stem cells. An intramural left ventricular pouch was fashioned after ligation of the left anterior descending artery in an athymic nude rat heterotopic heart transplant model. The bioartificial mixture (0.125 ml) was implanted in the infarcted area within the pouch. Echocardiography was performed to assess fractional shortening in: Group I, infarcted rats that received cell-matrix implants; Group II, rats given matrix implant without cells; Group III, rats given no matrix or cells; and Group IV, rats receiving transplanted hearts without ligation (n = 5/group). Hearts were stained for GFP, cardiac markers (connexin-43, α-sarcomeric actin), hematoxylin-eosin (H&E) and trichrome. Results: Embryonic stem cells formed stable intramyocardial grafts that were incorporated into the surrounding area without distorting myocardial geometry, thereby preventing ventricular wall thinning (anterior wall thickness was: Group I, 1.4 ± 0.1 mm; Group II, 1.0 ± 0.1 mm, Group III, 0.9 ± 0.2 mm; and Group IV, 1.3 ± 0.2 mm). The inoculated cells expressed connexin-43 and α-sarcomeric actin in vivo. Fractional shortening was better in embryonic stem cell-treated animals (Group I, 21.5 ± 3.5%; Group II, 12.4 ± 2.8%; Group III, 8.2 ± 2.9%; Group IV, 23.2 ± 4.2%). Conclusions: Embryonic stem cells are an efficient alternative substrate for myocardial tissue engineering and can prevent myocardial wall thinning and improve contractility after implantation into injured myocardium in a 3-dimensional matrix.

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