Determinants of Bioartificial Myocardial Graft Survival and Engraftment In Vivo

Knut Mueller-Stahl, Theo Kofidis, Payam Akhyari, Darren H.L. Lee, Andre Lenz, Eliana C. Martinez, Felix Woitek, Axel Haverich

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background: The specific interactions between tissue-engineered grafts and host tissue are frequently neglected. The aim of this study was to describe and quantify the fate of a tissue-engineered cardiac graft in vivo. Methods: Neonatal rat cardiomyocytes were cast into a collagen mesh, forming a bioartificial myocardial tissue (AMT). After 7 days in vitro, four groups were formed (Group A: sham; Group B: matrix; Group C: AMT [with additional host treatment with cyclosporine and prednisolone]; Group D: AMT; each n = 5) and the tissue grafts were implanted into the muscle pouch of adult rats at 14, 21 and 28 days. Implants were stained for troponin-T, BrdU, MF-20, desmin, vimentin, Flk-1, CD8, CD4, pentachrome, PSR and H&E. Results: AMT cell count, cell proportion, contractility, viability and metabolism proved stable in vitro. Grafted cells decreased over time and were detected in Group C until the end of the experiment (Day 28), and in Group D until Day 21. Angiogenesis began at the peripheries and slowly progressed toward the cores of the grafts. The thickness and collagen content of the matrix remained stable in Group C for 14 days, and decreased in all groups until Day 28 (thickness: Group B, -66%; Group C, -50%; Group D, -100%). Grafts were predominately infiltrated by macrophages and stromal cells, and less so by lymphocytes (Group D > B > C). Conclusion: The differentiation of cardiac and non-cardiac grafted cells, infiltrating cells, scaffold kinetics and angiogenesis showed host immune responses and degree of angiogenesis to be the determinants for AMT graft survival.

Original languageEnglish (US)
Pages (from-to)1242-1250
Number of pages9
JournalJournal of Heart and Lung Transplantation
Volume27
Issue number11
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Mueller-Stahl, K., Kofidis, T., Akhyari, P., Lee, D. H. L., Lenz, A., Martinez, E. C., Woitek, F., & Haverich, A. (2008). Determinants of Bioartificial Myocardial Graft Survival and Engraftment In Vivo. Journal of Heart and Lung Transplantation, 27(11), 1242-1250. https://doi.org/10.1016/j.healun.2008.08.003