title: Use of human umbilical cord blood-derived progenitor cells for tissue-engineered heart valves.
abstract: BACKGROUND
  Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept. Here we describe the use of cryopreserved umbilical cord blood-derived CD133(+) cells as a single cell source for the tissue engineering of heart valves.
  
  
  METHODS
  After expansion and differentiation of CD133(+) cells, phenotypes were analyzed by immunohistochemistry and cryopreserved. Heart valve scaffolds fabricated from a biodegradable polymer (n = 8) were seeded with blood-derived myofibroblasts and subsequently coated with blood-derived endothelial cells. Afterward, the heart valve constructs were grown in a pulse duplicator system. Analysis of all heart valves, including histology, immunohistochemistry, electron microscopy, fluorescence imaging, and biochemical and biomechanical examination, was performed.
  
  
  RESULTS
  The tissue-engineered heart valves showed endothelialized layered tissue formation including connective tissue between the inside and the outside of the scaffold. The notion of an intact endothelial phenotype was substantiated by fluorescence imaging studies of cellular nitric oxide production and Ca(2+) signaling. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer. Biochemical examination showed extracellular matrix formation (77% +/- 9% collagen of human pulmonary leaflet tissue [HPLT], 85% +/- 61% glycosaminoglycans of HPLT and 67% +/- 17% elastin of HPLT).
  
  
  CONCLUSIONS
  Importantly, this study demonstrates in vitro generation of viable human heart valves based on CD133(+) cells derived from umbilical cord blood. These findings constitute a significant step forward in the development of new clinical strategies for the treatment of congenital defects.
authors.affiliation: Department of Cardiovascular Surgery, Ludwig-Maximilians-University, Munich, Germany. ralf.sodian@med.uni-muenchen.de
authors.forename: Ralf
authors.initials: R
authors.lastname: Sodian
authors.forename: Philipp
authors.initials: P
authors.lastname: Schaefermeier
authors.forename: Sybille
authors.initials: S
authors.lastname: Abegg-Zips
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.forename: Mehdi
authors.initials: M
authors.lastname: Shakibaei
authors.forename: Sabine
authors.initials: S
authors.lastname: Daebritz
authors.forename: Johannes
authors.initials: J
authors.lastname: Ziegelmueller
authors.forename: Christoph
authors.initials: C
authors.lastname: Schmitz
authors.forename: Bruno
authors.initials: B
authors.lastname: Reichart
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000032:analysis; D001696:Biomechanical Phenomena; D002478:Cells, Cultured; D015925:Cryopreservation; D004727:Endothelium / Q000166:cytology; D005109:Extracellular Matrix / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology*; D005347:Fibroblasts / Q000166:cytology; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis; D006351:Heart Valves / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D006801:Humans; D008854:Microscopy, Electron; D010455:Peptides / Q000032:analysis; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides