title: Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts.
abstract: BACKGROUND
  Cardiac cell transplantation is limited by poor graft viability. We aimed to enhance the survival of transplanted cardiomyoblasts using growth factor-supplemented collagen matrices.
  
  
  RESULTS
  H9c2 cardiomyoblasts were lentivirally transduced to express firefly luciferase and green fluorescent protein (GFP). Lewis rats underwent ligation of the left anterior descending artery (LAD) ligation to induce an anterior wall myocardial infarction. Hearts (n=9/group) were harvested and restored ex vivo with 1 x 10(6) genetically labeled H9c2 cells either in (1) saline-suspension, or seeded onto (2) collagen-matrix (Gelfoam [GF];), (3) GF/Matrigel (GF/MG), (4) GF/MG/VEGF (10 microg/mL), or (5) GF/MG/FGF (10 microg/mL). Hearts were then abdominally transplanted into syngeneic recipients (working heart model). Controls (n=6/group) underwent infarction followed by GF implantation or saline injection. Cell survival was evaluated using optical bioluminescence on days 1, 5, 8, 14, and 28 postoperatively. At 4 weeks, fractional shortening and ejection fraction were determined using echocardiography and magnetic resonance imaging, respectively. Graft characteristics were assessed by immunohistology. Bioluminescence signals on days 5, 8, and 14 were higher for GF-based grafts compared with plain H9c2 injections (P<0.03). Signals were higher for GF/MG grafts compared with GF alone (P<0.02). GFP-positive, spindle-shaped H9c2 cells were found integrated in the infarct border zones at day 28. Left ventricular (LV) function of hearts implanted with collagen-based grafts was better compared with controls (P<0.05). Vascular endothelial growth factor or fibroblast growth factor did not further improve graft survival or heart function.
  
  
  CONCLUSIONS
  Collagen matrices enhance early survival of H9c2 cardiomyoblasts after transplantation into ischemic hearts and lead to improved LV function. Further optimization of the graft design should make restoration of large myocardial infarctions by tissue engineering approaches effective.
authors.affiliation: Department of Cardiothoracic Surgery, Stanford University, School of Medicine, Stanford, California, USA. ingo.kutschka@t-online.de
authors.forename: Ingo
authors.initials: I
authors.lastname: Kutschka
authors.forename: Ian Y
authors.initials: IY
authors.lastname: Chen
authors.forename: Theo
authors.initials: T
authors.lastname: Kofidis
authors.forename: Takayasu
authors.initials: T
authors.lastname: Arai
authors.forename: Georges
authors.initials: G
authors.lastname: von Degenfeld
authors.forename: Ahmad Y
authors.initials: AY
authors.lastname: Sheikh
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Hendry
authors.forename: Jeremy
authors.initials: J
authors.lastname: Pearl
authors.forename: Grant
authors.initials: G
authors.lastname: Hoyt
authors.forename: Ramachadra
authors.initials: R
authors.lastname: Sista
authors.forename: Phillip C
authors.initials: PC
authors.lastname: Yang
authors.forename: Helen M
authors.initials: HM
authors.lastname: Blau
authors.forename: Sanjiv S
authors.initials: SS
authors.lastname: Gambhir
authors.forename: Robert C
authors.initials: RC
authors.lastname: Robbins
mesh_terms: D034841:Abdominal Cavity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003094:Collagen / Q000494:pharmacology*; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000637:transplantation*; D005346:Fibroblast Growth Factors / Q000494:pharmacology; D005781:Gelatin Sponge, Absorbable; D017930:Genes, Reporter; D006085:Graft Survival / Q000187:drug effects*; D016027:Heart Transplantation; D020007:Implants, Experimental; D007797:Laminin; D008279:Magnetic Resonance Imaging; D008297:Male; D032446:Myoblasts / Q000637:transplantation*; D009200:Myocardial Contraction; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery*; D032383:Myocytes, Cardiac / Q000637:transplantation*; D011509:Proteoglycans; D051381:Rats; D011917:Rats, Inbred Lew; D013318:Stroke Volume; D023822:Tissue Engineering / Q000379:methods; D014161:Transduction, Genetic; D016042:Transplantation, Heterotopic; D014185:Transplantation, Isogeneic; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D016277:Ventricular Function, Left
chemical_list: D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D005346:Fibroblast Growth Factors; D003094:Collagen