title: Intravital molecular imaging of small-diameter tissue-engineered vascular grafts in mice: a feasibility study.
abstract: OBJECTIVE
  Creating functional small-diameter tissue-engineered blood vessels has not been successful to date. Moreover, the processes underlying the in vivo remodeling of these grafts and the fate of cells seeded onto scaffolds remain unclear. Here we addressed these unmet scientific needs by using intravital molecular imaging to monitor the development of tissue-engineered vascular grafts (TEVG) implanted in mouse carotid artery.
  
  
  RESULTS
  Green fluorescent protein-labeled human bone marrow-derived mesenchymal stem cells and cord blood-derived endothelial progenitor cells were seeded on polyglycolic acid-poly-L-lactic acid scaffolds to construct small-caliber TEVG that were subsequently implanted in the carotid artery position of nude mice (n = 9). Mice were injected with near-infrared agents and imaged using intravital fluorescence microscope at 0, 7, and 35 days to validate in vivo the TEVG remodeling capability (Prosense680; VisEn, Woburn, MA) and patency (Angiosense750; VisEn). Imaging coregistered strong proteolytic activity and blood flow through anastomoses at both 7 and 35 days postimplantation. In addition, image analyses showed green fluorescent protein signal produced from mesenchymal stem cell up to 35 days postimplantation. Comprehensive correlative histopathological analyses corroborated intravital imaging findings.
  
  
  CONCLUSIONS
  Multispectral imaging offers simultaneous characterization of in vivo remodeling enzyme activity, functionality, and cell fate of viable small-caliber TEVG.
authors.affiliation: Center for Molecular Imaging Research , Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jesper
authors.initials: J
authors.lastname: Hjortnaes
authors.forename: Danielle
authors.initials: D
authors.lastname: Gottlieb
authors.forename: Jose-Luiz
authors.initials: JL
authors.lastname: Figueiredo
authors.forename: Juan
authors.initials: J
authors.lastname: Melero-Martin
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Kohler
authors.forename: Joyce
authors.initials: J
authors.lastname: Bischoff
authors.forename: Ralph
authors.initials: R
authors.lastname: Weissleder
authors.forename: John E
authors.initials: JE
authors.lastname: Mayer
authors.forename: Elena
authors.initials: E
authors.lastname: Aikawa
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D005240:Feasibility Studies; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D057054:Molecular Imaging / Q000379:methods*; D011091:Polyesters; D011100:Polyglycolic Acid / Q000494:pharmacology; D011108:Polymers / Q000494:pharmacology; D019919:Prosthesis Implantation; D015203:Reproducibility of Results; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry; D014162:Transfection
chemical_list: D011091:Polyesters; D011108:Polymers; D049452:Green Fluorescent Proteins; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)