Instant MR labeling of stem cells using magnetoelectroporation

For cellular MR imaging, conventional approaches to intracellular magnetic labeling of nonphagocytic cells rely on the use of secondary compounds such as transfection agents and prolonged incubation of cells. Magnetoelectroporation (MEP) was investigated as an alternative method to achieve instant (<1 s) endosomal labeling with the FDA‐approved formulation Feridex, without the need for adjunct agents or initiating cell cultures. While MEP was harmful at higher voltages or pulse durations, the procedure could be properly calibrated using a pulse of 130 V and 17 ms. Labeling was demonstrated for stem cells from mice, rats, and humans; the uptake of iron was in the picogram range and comparable to values obtained using transfection agents. MEP‐labeled stem cells exhibited an unaltered viability, proliferation, and mitochondrial metabolic rate. Labeled mesenchymal stem cells (MSCs) and neural stem cells (NSCs) differentiated into adipogenic, osteogenic, and neural lineages in an identical fashion as unlabeled cells, while containing Feridex particles as demonstrated by double immunofluorescent staining. MEP‐labeled NSCs proliferated normally following intrastriatal transplantation and could be readily detected by MR imaging in vivo. As MEP circumvents the use of secondary agents, obviating the need for clinical approval, MEP labeling may be ideally suitable for bedside implementation. Magn Reson Med, 2005. © 2005 Wiley‐Liss, Inc.

[1]  Mathias Hoehn,et al.  Monitoring of implanted stem cell migration in vivo: A highly resolved in vivo magnetic resonance imaging investigation of experimental stroke in rat , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[2]  Heather Kalish,et al.  Efficient magnetic cell labeling with protamine sulfate complexed to ferumoxides for cellular MRI. , 2004, Blood.

[3]  R Weissleder,et al.  High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. , 1999, Bioconjugate chemistry.

[4]  Alan P Koretsky,et al.  MRI detection of single particles for cellular imaging. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[5]  Jeff W M Bulte,et al.  Hot spot MRI emerges from the background , 2005, Nature Biotechnology.

[6]  J. Bulte,et al.  Sensitive NMR detection of cationic-polymer-based gene delivery systems using saturation transfer via proton exchange. , 2001, Journal of the American Chemical Society.

[7]  C. Cepko,et al.  Establishment and characterization of multipotent neural cell lines using retrovirus vector-mediated oncogene transfer. , 1990, Journal of neurobiology.

[8]  Alan P Koretsky,et al.  Sizing it up: Cellular MRI using micron‐sized iron oxide particles , 2005, Magnetic resonance in medicine.

[9]  Peter van Gelderen,et al.  Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells , 2001, Nature Biotechnology.

[10]  E. Rummeny,et al.  In vivo tracking of genetically engineered, anti-HER2/neu directed natural killer cells to HER2/neu positive mammary tumors with magnetic resonance imaging , 2004, European Radiology.

[11]  M. Pittenger,et al.  Multilineage potential of adult human mesenchymal stem cells. , 1999, Science.

[12]  Mangay Williams,et al.  Superparamagnetic iron oxide particles transactivator protein-fluorescein isothiocyanate particle labeling for in vivo magnetic resonance imaging detection of cell migration: uptake and durability , 2003, Transplantation.

[13]  C. Cepko,et al.  Multipotent neural cell lines can engraft and participate in development of mouse cerebellum , 1992, Cell.

[14]  E. Neumann,et al.  Gene transfer into mouse lyoma cells by electroporation in high electric fields. , 1982, The EMBO journal.

[15]  Jeff W M Bulte,et al.  Monitoring cell therapy using iron oxide MR contrast agents. , 2004, Current pharmaceutical biotechnology.

[16]  J A Frank,et al.  Neurotransplantation of magnetically labeled oligodendrocyte progenitors: magnetic resonance tracking of cell migration and myelination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[17]  Alan P Koretsky,et al.  Highly efficient endosomal labeling of progenitor and stem cells with large magnetic particles allows magnetic resonance imaging of single cells. , 2003, Blood.

[18]  J. Bulte,et al.  Preparation of magnetically labeled cells for cell tracking by magnetic resonance imaging. , 2004, Methods in enzymology.

[19]  Jeff W M Bulte,et al.  Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. , 2003, Radiology.