title: Optimizing engineered heart tissue for therapeutic applications as surrogate heart muscle.
abstract: BACKGROUND
  Cardiac tissue engineering aims at providing heart muscle for cardiac regeneration. Here, we hypothesized that engineered heart tissue (EHT) can be improved by using mixed heart cell populations, culture in defined serum-free and Matrigel-free conditions, and fusion of single-unit EHTs to multi-unit heart muscle surrogates.
  
  
  RESULTS
  EHTs were constructed from native and cardiac myocyte enriched heart cell populations. The former demonstrated a superior contractile performance and developed vascular structures. Peptide growth factor-supplemented culture medium was developed to maintain contractile EHTs in a serum-free environment. Addition of triiodothyronine and insulin facilitated withdrawal of Matrigel from the EHT reconstitution mixture. Single-unit EHTs could be fused to form large multi-unit EHTs with variable geometries.
  
  
  CONCLUSIONS
  Simulating a native heart cell environment in EHTs leads to improved function and formation of primitive capillaries. The latter may constitute a preformed vascular bed in vitro and facilitate engraftment in vivo. Serum- and Matrigel-free culture conditions are expected to reduce immunogenicity of EHT. Fusion of single-unit EHT allows production of large heart muscle constructs that may eventually serve as optimized tissue grafts in cardiac regeneration in vivo.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 5, 20246 Hamburg, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Naito
authors.forename: Ivan
authors.initials: I
authors.lastname: Melnychenko
authors.forename: Michael
authors.initials: M
authors.lastname: Didié
authors.forename: Karin
authors.initials: K
authors.lastname: Schneiderbanger
authors.forename: Pia
authors.initials: P
authors.lastname: Schubert
authors.forename: Stephan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Thomas
authors.initials: T
authors.lastname: Eschenhagen
authors.forename: Wolfram-Hubertus
authors.initials: WH
authors.lastname: Zimmermann
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002196:Capillaries / Q000166:cytology; D002478:Cells, Cultured / Q000166:cytology / Q000187:drug effects; D002642:Chick Embryo; D003094:Collagen; D003470:Culture Media / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006133:Growth Substances / Q000494:pharmacology; D006321:Heart / Q000502:physiology; D006736:Horses; D007328:Insulin / Q000494:pharmacology; D007797:Laminin; D009024:Morphogenesis; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects; D011509:Proteoglycans; D051381:Rats; D012038:Regeneration / Q000502:physiology; D044967:Serum; D023822:Tissue Engineering / Q000379:methods*; D014020:Tissue Extracts / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology
chemical_list: D003470:Culture Media; D016895:Culture Media, Serum-Free; D004338:Drug Combinations; D006133:Growth Substances; D007328:Insulin; D007797:Laminin; D011509:Proteoglycans; D014020:Tissue Extracts; D014284:Triiodothyronine; C059485:matrigel; D003094:Collagen