Self-assembling peptide nanofibers and skeletal myoblast transplantation in infarcted myocardium.
Cell transplantation is currently limited by poor graft retention and survival in the postinfarction scar. Because this issue could potentially be addressed by embedding cells in bioinjectable scaffolds and boosting cell survival pathways, we induced a myocardial infarction in 72 rats to assess the effects of different self-assembling peptides with or without platelet-derived growth factor (PDGF-BB) on survival of transplanted skeletal myoblasts. Two weeks after coronary artery ligation, rats were randomized to receive in-scar injections of culture medium (controls, n = 11), self-assembling peptide (RAD16-I) nanofibers (NF, n = 9), skeletal myoblasts (n = 12), or skeletal myoblasts in combination with NF (n = 8). In separate experiments with different self-assembling peptides (RAD16-II), rats received in-scar injections of culture medium (controls, n = 6), skeletal myoblasts (n = 10), PDGF-loaded peptides (n = 7), or skeletal myoblasts (5 x 10(6)) in combination with PDGF-loaded peptides (n = 9). After 1 month, left ventricular function, as assessed by echocardiography, was not improved in either of the experimental groups compared with controls. This correlated with the failure of RAD16-I peptides or PDGF-loaded RAD16-II peptides to improve myoblast survival despite a greater angiogenesis. In vitro experiments confirmed that the number of myoblasts decreased over time when seeded on nanofiber gels. These data suggest that the optimal use of biomaterial scaffolds for survival of transplanted cells will require specific tailoring of the biomaterial to the cell type.
Dubois
Gilbert
G
Assistance Publique-Hôpitaux de Paris, Ecole de Chirurgie, Paris 75005, France.
Segers
Vincent F M
VF
Bellamy
Valérie
V
Sabbah
Laurent
L
Peyrard
Séverine
S
Bruneval
Patrick
P
Hagège
Albert A
AA
Lee
Richard T
RT
Menasché
Philippe
P
D000818:Animals; D000077214:Becaplermin; D017690:Cell Transplantation; D032448:Myoblasts, Skeletal / Q000637:transplantation*; D009203:Myocardial Infarction / Q000628:therapy*; D049329:Nanostructures / Q000627:therapeutic use*; D010455:Peptides / Q000627:therapeutic use*; D010982:Platelet-Derived Growth Factor / Q000627:therapeutic use; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017211:Treatment Failure; D016896:Treatment Outcome; D016277:Ventricular Function, Left
D010455:Peptides; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin