The real estate of myoblast cardiac transplantation: negative remodeling is associated with location.
BACKGROUND
Skeletal myoblast transplantation has been proposed as a therapy for ischemic cardiomyopathy owing to its possible role in myogenesis. The relative safety and efficacy based on location within scar is not known. We hypothesized that skeletal myoblasts transplanted into peripheral scar (compared with central scar) would more effectively attenuate negative left ventricular (LV) remodeling but at the risk of arrhythmia.


METHODS
New Zealand White rabbits (n = 34) underwent mid-left anterior descending artery (LAD) ligation to produce a transmural LV infarction. One month after LAD ligation, skeletal myoblasts were injected either in the scar center (n = 13) or scar periphery (n = 10) and compared with saline injection (n = 11). Holter monitoring and magnetic resonance imaging (MRI) was performed pre-injection; Holter monitoring was continued until 2 weeks after injection, with follow-up MRI at 1 month.


RESULTS
The centrally treated animals demonstrated increased LV end-systolic volume, end-diastolic volume, and mass that correlated with the number of injected cells. There was a trend toward attenuation of negative LV remodeling in peripherally treated animals compared with vehicle. Significant late ectopy was seen in several centrally injected animals, with no late ectopy seen in peripherally injected animals.


CONCLUSIONS
We noted untoward effects with respect to negative LV remodeling after central injection, suggesting that transplanted cell location with respect to scar may be a key factor in the safety and efficacy of skeletal myoblast cardiac transplantation. Administration of skeletal myoblasts into peripheral scar appears safe, with a trend toward improved function in comparison with sham injection.
McCue
Jonathan D
JD
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Swingen
Cory
C
Feldberg
Tanya
T
Caron
Gabe
G
Kolb
Adam
A
Denucci
Christopher
C
Prabhu
Somnath
S
Motilall
Randy
R
Breviu
Brian
B
Taylor
Doris A
DA
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016027:Heart Transplantation / Q000379:methods*; D008279:Magnetic Resonance Imaging; D008297:Male; D032446:Myoblasts / Q000637:transplantation*; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000473:pathology / Q000601:surgery*; D009206:Myocardium / Q000166:cytology*; D011817:Rabbits; D013318:Stroke Volume / Q000502:physiology; D016896:Treatment Outcome; D020257:Ventricular Remodeling / Q000502:physiology*