Embryonic stem cell grafting in normal and infarcted myocardium: serial assessment with MR imaging and PET dual detection.
OBJECTIVE
To use magnetic resonance (MR) imaging and positron emission tomography (PET) dual detection of cardiac-grafted embryonic stem cells (ESCs) to examine (a) survival and proliferation of ESCs in normal and infarcted myocardium, (b) host macrophage versus grafted ESC contribution to serial MR imaging signal over time, and (c) cardiac function associated with the formation of grafts and whether improvement in cardiac function is related to cardiac differentiation of ESCs.


METHODS
All animal procedures were approved by the institutional animal care and use committee. Murine ESCs were stably transfected with a mutant version of herpes simplex virus type 1 thymidine kinase, HSV1-sr39tk, and also were labeled with superparamagnetic iron oxide (SPIO) particles. Cells were injected directly in the border zone of the infarcted heart or in corresponding regions of normal hearts in athymic rats. PET and MR imaging were performed longitudinally for 4 weeks in the same animals.


RESULTS
ESCs survived and underwent proliferation in the infarcted and normal hearts, as demonstrated by serial increases in 9-(4-[(18)F]fluoro-3-hydroxymethylbutyl) guanine PET signals. In parallel, the hypointense areas on MR images at the injection sites decreased over time. Double staining for host macrophages and SPIO particles revealed that the majority of SPIO-containing cells were macrophages at week 4 after injection. Left ventricular ejection fraction increased in the ESC-treated rats but decreased in culture media-treated rats, and border-zone function was preserved in ESC-treated animals; however, cardiac differentiation of ESCs was less than 0.5%.


CONCLUSIONS
Dual-modality imaging permits complementary information in regard to cell survival and proliferation, graft formation, and effects on cardiac function.


BACKGROUND
http://radiology.rsnajnls.org/cgi/content/full/250/3/821/DC1.
Qiao
Hui
H
Department of Radiology, University of Pennsylvania, B6 Blockley Hall, MC 6069, 422 Curie Blvd, Philadelphia, PA 19104, USA.
Zhang
Hualei
H
Zheng
Yuanjie
Y
Ponde
Datta E
DE
Shen
Dinggang
D
Gao
Fabao
F
Bakken
Ashley B
AB
Schmitz
Alexander
A
Kung
Hank F
HF
Ferrari
Victor A
VA
Zhou
Rong
R
D000818:Animals; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000000981:diagnostic imaging / Q000473:pathology / Q000637:transplantation; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009203:Myocardial Infarction / Q000175:diagnosis* / Q000601:surgery*; D049268:Positron-Emission Tomography / Q000379:methods*; D051381:Rats; D011923:Rats, Nude; D013382:Subtraction Technique; D016896:Treatment Outcome