title: Undifferentiated mesenchymal stem cells seeded on a vascular prosthesis contribute to the restoration of a physiologic vascular wall.
abstract: BACKGROUND
  We evaluated the possibility of restoring a physiologic vascular wall using undifferentiated mesenchymal stem cells (MSCs) seeded on a polyurethane vascular prosthesis.
  
  
  METHODS
  Undifferentiated MSCs were seeded on a vascular prosthesis and implanted into Wistar male rats (weight, 350 g) to investigate differentiation into smooth muscle cells and to determine graft endothelialization in vivo.
  
  
  RESULTS
  Seeded or nonseeded grafts were surgically implanted. Undifferentiated MSCs were first labelled for green fluorescent protein. After 2 weeks in vivo, MSC that were initially self-expanded on the graft in a monolayer were organized in a multicellular layer mimicking media of aortic adjacent wall. They coexpressed green fluorescent protein and smooth muscle proteins that were not present before the in vivo engraftment, indicating that in vivo conditions induced smooth muscle protein maturation. Undifferentiated MSC showed an electrophysiologic profile quite different than mature smooth muscle cells. In both in vitro- and in vivo-differentiated MSCs, adenosine triphosphate, an IP(3)-dependent agonist, induced an increase in calcium similar to that which occurred in mature smooth muscle cells. However, MSCs failed to respond to caffeine, a ryanodine receptor activator, indicating the absence of mature calcium signaling, and finally, contraction was absent. Endothelialization attested by immunohistology and scanning electron microscopy was greater in MSC-seeded grafts that prevent thrombosis.
  
  
  CONCLUSIONS
  Only partial smooth muscle cell differentiation of MSCs resulted when seeded on vascular grafts, but MSCs spontaneously restore a media-like thick wall. Mesenchymal stem cells have a positive impact on in vivo endothelialization in rats that supports their potential for use in vascular surgery.
  
  
  CONCLUSIONS
  Thrombosis of vascular prostheses is a major complication of surgery. We showed on rat aorta that mesenchymal stem cells seeded on polyurethane patch restore endothelium. It also induced incomplete smooth muscle differentiation. In the future, stem cell could prevent thrombosis of vascular prostheses.
authors.affiliation: Labpart EA 3852, Cardiac and Vascular Surgery Department, CHU Trousseau Tourq, Tours, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Mirza
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Hyvelin
authors.forename: Gael Y
authors.initials: GY
authors.lastname: Rochefort
authors.forename: Patrick
authors.initials: P
authors.lastname: Lermusiaux
authors.forename: Daniel
authors.initials: D
authors.lastname: Antier
authors.forename: Bonaventure
authors.initials: B
authors.lastname: Awede
authors.forename: Pierre
authors.initials: P
authors.lastname: Bonnet
authors.forename: Jorge
authors.initials: J
authors.lastname: Domenech
authors.forename: Veronique
authors.initials: V
authors.lastname: Eder
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000601:surgery* / Q000648:ultrastructure; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000295:instrumentation*; D002110:Caffeine / Q000494:pharmacology; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism / Q000601:surgery; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000601:surgery; D010641:Phenotype; D011140:Polyurethanes; D011474:Prosthesis Design; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014162:Transfection; D014661:Vasoconstriction
chemical_list: D009124:Muscle Proteins; D011140:Polyurethanes; D049452:Green Fluorescent Proteins; D002110:Caffeine; D000255:Adenosine Triphosphate