title: Autologous valve replacement-CD133+ stem cell-plus-fibrin composite-based sprayed cell seeding for intraoperative heart valve tissue engineering.
abstract: OBJECTIVE
  The development of biological valve prostheses with lifetime native-like performance and optimal host engraftment is an ultimate goal of heart valve tissue engineering. We describe a new concept for autologous graft coating based on a CD133(+)-stem-cells-plus-fibrin (SC+F) complex processed from bone marrow and peripheral blood of a single patient.
  
  
  METHODS
  CD133(+)-SC (1 × 10(6) cells/mL) from human bone marrow and autologous fibrin (20 mg/mL) were administered simultaneously via spray administration using the novel Vivostat Co-Delivery System. During static cultivation, SC+F performance was monitored for 20 days after delivery and compared with controls. For dynamic testing SC+F-composite was sprayed on a decellularized porcine pulmonary valve and transferred to a bioreactor under pulsatile flow conditions for 7 days.
  
  
  RESULTS
  Static cultivation of SC+F-composite induced significant improvements in stem cell proliferation as compared with controls. For dynamic testing, microscopic analyses on a smooth engineered heart valve surface detected homogenous distribution of stem cells. Ultrasonic analysis revealed native-like valve performance. Applied CD133(+) stem cells differentiated into endothelial-like cells positive for CD31 and vascular endothelial growth factor receptor 2 and engrafted the valve. However, occasional delamination was observed.
  
  
  CONCLUSIONS
  SC+F serves as an excellent autologous matrix for intraoperative tissue engineering of valve prostheses promising optimal in vivo integration. However, stability remains an issue.
authors.affiliation: Reference and Translation Center for Cardiac Stem Cell Therapy, University of Rostock, Rostock, Germany. alexander.kaminski@med.uni-rostock.de
authors.forename: Alexander
authors.initials: A
authors.lastname: Kaminski
authors.forename: Christian
authors.initials: C
authors.lastname: Klopsch
authors.forename: Peter
authors.initials: P
authors.lastname: Mark
authors.forename: Can
authors.initials: C
authors.lastname: Yerebakan
authors.forename: Peter
authors.initials: P
authors.lastname: Donndorf
authors.forename: Ralf
authors.initials: R
authors.lastname: Gäbel
authors.forename: Friederike
authors.initials: F
authors.lastname: Eisert
authors.forename: Stefan
authors.initials: S
authors.lastname: Hasken
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreitz
authors.forename: Aenne
authors.initials: A
authors.lastname: Glass
authors.forename: Stefan
authors.initials: S
authors.lastname: Jockenhövel
authors.forename: Nan
authors.initials: N
authors.lastname: Ma
authors.forename: Guenther
authors.initials: G
authors.lastname: Kundt
authors.forename: Andreas
authors.initials: A
authors.lastname: Liebold
authors.forename: Gustav
authors.initials: G
authors.lastname: Steinhoff
mesh_terms: D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology; D005337:Fibrin / Q000494:pharmacology*; D006023:Glycoproteins / Q000378:metabolism*; D006350:Heart Valve Prosthesis; D006801:Humans; D007430:Intraoperative Care; D008422:Materials Testing; D010455:Peptides / Q000378:metabolism*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D005337:Fibrin