Collagen matrices enhance survival of transplanted cardiomyoblasts and contribute to functional improvement of ischemic rat hearts.
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.
Kutschka
Ingo
I
Department of Cardiothoracic Surgery, Stanford University, School of Medicine, Stanford, California, USA. ingo.kutschka@t-online.de
Chen
Ian Y
IY
Kofidis
Theo
T
Arai
Takayasu
T
von Degenfeld
Georges
G
Sheikh
Ahmad Y
AY
Hendry
Stephen L
SL
Pearl
Jeremy
J
Hoyt
Grant
G
Sista
Ramachadra
R
Yang
Phillip C
PC
Blau
Helen M
HM
Gambhir
Sanjiv S
SS
Robbins
Robert C
RC
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
D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D005346:Fibroblast Growth Factors; D003094:Collagen