Impact of magnetic labeling on human and mouse stem cells and their long-term magnetic resonance tracking in a rat model of Parkinson disease.
Magnetic resonance imaging (MRI) of magnetically labeled stem cells has become a valuable tool in the understanding and evaluation of experimental stem cell-based therapies of degenerative central nervous system disorders. This comprehensive study assesses the impact of magnetic labeling of both human and rodent stem cell-containing populations on multiple biologic parameters as maintenance of stemness and oxidative stress levels. Cells were efficiently magnetically labeled with very small superparamagnetic iron oxide particles. Only under the condition of tailored labeling strategies can the impact of magnetic labeling on vitality, proliferation, pluripotency, and oxidative stress levels be minimized. In a rat model of Parkinson disease, magnetically labeled mouse embryonic stem cells were tracked by high-field MRI for 6 months. Significant interindividual differences concerning the spatial distribution of cells became evident. Histologically, transplanted green fluorescent protein-positive iron oxide-labeled cells were clearly identified. No significant increase in oxidative stress levels at the implantation site and no secondary uptake of magnetic label by host phagocytotic cells were observed. Our study strongly suggests that molecular MRI approaches must be carefully tailored to the respective cell population to exert minimal physiologic impact, ensuring the feasibility of this imaging approach for clinical applications.
Stroh
Albrecht
A
Institute of Neuroscience, Technical University Munich, Munich, Germany. albrecht.stroh@lrz.tum.de
Boltze
Johannes
J
Sieland
Katharina
K
Hild
Katharina
K
Gutzeit
Cindy
C
Jung
Tobias
T
Kressel
Jenny
J
Hau
Susann
S
Reich
Doreen
D
Grune
Tilman
T
Zimmer
Claus
C
D000818:Animals; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000637:transplantation*; D005290:Ferric Compounds / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008280:Magnetics / Q000379:methods*; D051379:Mice; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D051381:Rats; D012680:Sensitivity and Specificity; D013194:Staining and Labeling / Q000379:methods*; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation
D005290:Ferric Compounds; C000499:ferric oxide