Multimodality evaluation of the viability of stem cells delivered into different zones of myocardial infarction.
BACKGROUND
We tested the hypothesis that multimodality imaging of mouse embryonic stem cells (mESCs) provides accurate assessment of cellular location, viability, and restorative potential after transplantation into different zones of myocardial infarction.


RESULTS
Mice underwent left anterior descending artery ligation followed by transplantation of dual-labeled mESCs with superparamagnetic iron oxide and luciferase via direct injection into 3 different zones of myocardial infarction: intra-infarction, peri-infarction, and normal (remote). One day after transplantation, magnetic resonance imaging enabled assessment of the precise anatomic locations of mESCs. Bioluminescence imaging allowed longitudinal analysis of cell viability through detection of luciferase activity. Subsequent evaluation of myocardial regeneration and functional restoration was performed by echocardiography and pressure-volume loop analysis. Using 16-segment analysis, we demonstrated precise localization of dual-labeled mESCs. A strong correlation between histology and magnetic resonance imaging was established (r=0.962, P=0.002). Bioluminescent imaging data demonstrated that cell viability in the remote group was significantly higher than in other groups. Echocardiography and pressure-volume loop analysis revealed improved functional restoration in animals treated with mESCs, although myocardial regeneration was not observed.


CONCLUSIONS
Multimodality evaluation of mESC engraftment in the heterogeneous tissue of myocardial infarction is possible. Magnetic resonance imaging demonstrated accurate anatomic localization of dual-labeled mESCs. Bioluminescent imaging enabled assessment of variable viability of mESCs transplanted into the infarcted myocardium. Echocardiography and pressure-volume loop analysis validated the restorative potential of mESCs. Although mESCs transplanted into the remote zone demonstrated the highest viability, precise delivery of mESCs into the peri-infarction region might be equally critical in restoring the injured myocardium.
Hung
Ta-Chuan
TC
Division of Cardiovascular Medicine, Stanford University, Stanford, Calif 94305-5233, USA.
Suzuki
Yoriyasu
Y
Urashima
Takashi
T
Caffarelli
Anthony
A
Hoyt
Grant
G
Sheikh
Ahmad Y
AY
Yeung
Alan C
AC
Weissman
Irving
I
Robbins
Robert C
RC
Bulte
Jeff W M
JW
Bulte
Jeff M
JM
Yang
Phillip C
PC
D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D003287:Contrast Media; D003911:Dextrans; D004195:Disease Models, Animal; D004452:Echocardiography; D053595:Embryonic Stem Cells / Q000637:transplantation*; D005240:Feasibility Studies; D005260:Female; D052203:Ferrosoferric Oxide; D008156:Luciferases / Q000235:genetics; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D020127:Recovery of Function; D012038:Regeneration; D033581:Stem Cell Transplantation; D013997:Time Factors; D014162:Transfection; D016277:Ventricular Function, Left; D017725:Ventricular Pressure
D003287:Contrast Media; D003911:Dextrans; D058185:Magnetite Nanoparticles; D008156:Luciferases; C065507:ferumoxides; D052203:Ferrosoferric Oxide