Optimization of magnetosonoporation for stem cell labeling.
Recent advances in magnetic cell labeling have taken place with the development of a magnetosonoporation (MSP) technique. The aim of this study was to optimize the MSP protocol in order to achieve high cell viability and intracellular uptake of MR contrast agents. First, we determined the sub-optimal MSP parameters by evaluating the viabilities of C17.2 neural stem cells without Feridex using various MSP intensities ranging from 0.1 to 1 w/cm(2), duty cycles at 20%, 50% or 100%, and exposure times from 1-15 min. The sub-optimized MSP parameters with cell viabilities greater than 90% were further optimized by evaluating both cell viability and intracellular iron uptake when Feridex was used. We then used the optimized MSP parameters to determinate the optimal concentration of Feridex for magnetic cell labeling. Subsequently, we validated the feasibility of using MRI to track the migration of neural stem cells from the transplanted sites to glioma masses in four mouse brains when the cells had been labeled with Feridex using the optimized MSP protocol. The MRI findings were confirmed by histological correlations. In vitro experiments demonstrated that the optimal MSP protocol was achieved at 20% duty cycle, 0.3 w/cm(2) ultrasound intensity, 5-min exposure time and 1 mg/mL Feridex. This study demonstrated that the optimized MSP cell labeling technique can achieve both high cell viability and intracellular uptake of MR contrast agents, and has the potential to be a useful cell labeling technique to facilitate future clinical translation of MRI-integrated cell therapy.
Xie
Daohai
D
Image-Guided Bio-Molecular Interventions Section, Department of Radiology, University of Washington School of Medicine, Seattle, WA 98195, USA.
Qiu
Bensheng
B
Walczak
Piotr
P
Li
Xubin
X
Ruiz-Cabello
Jesus
J
Minoshima
Satoshi
S
Bulte
Jeff W M
JW
Yang
Xiaoming
X
D000818:Animals; D002465:Cell Movement; D002470:Cell Survival; D003911:Dextrans; D018274:Electroporation / Q000379:methods*; D052203:Ferrosoferric Oxide / Q000378:metabolism; D005910:Glioma / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008280:Magnetics / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D013194:Staining and Labeling / Q000379:methods*; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014465:Ultrasonics
D003911:Dextrans; D058185:Magnetite Nanoparticles; D007501:Iron; C065507:ferumoxides; D052203:Ferrosoferric Oxide