Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells

Jeff W Bulte, Trevor Douglas, Brian Witwer, Su Chun Zhang, Erica Strable, Bobbi K. Lewis, Holly Zywicke, Brad Miller, Peter Van Gelderen, Bruce M. Moskowitz, Ian D. Duncan, Joseph A. Frank

Research output: Contribution to journalArticle

Abstract

Magnetic resonance (MR) tracking of magnetically labeled stem and progenitor cells is an emerging technology, leading to an urgent need for magnetic probes that can make cells highly magnetic during their normal expansion in culture. We have developed magnetodendrimers as a versatile class of magnetic tags that can efficiently label mammalian cells, including human neural stem cells (NSCs) and mesenchymal stem cells (MSCs), through a nonspecific membrane adsorption process with subsequent intracellular (non-nuclear) localization in endosomes. The superparamagnetic iron oxide nanocomposites have been optimized to exhibit superior magnetic properties and to induce sufficient MR cell contrast at incubated doses as low as 1 μg iron/ml culture medium. When containing between 9 and 14 pg iron/cell, labeled cells exhibit an ex vivo nuclear magnetic resonance (NMR) relaxation rate (1/T2) as high as 24-39 s-1/mM iron. Labeled cells are unaffected in their viability and proliferating capacity, and labeled human NSCs differentiate normally into neurons. Furthermore, we show here that NSC-derived (and LacZ-transfected), magnetically labeled oligodendroglial progenitors can be readily detected in vivo at least as long as six weeks after transplantation, with an excellent correlation between the obtained MR contrast and staining for β-galactosidase expression. The availability of magnetodendrimers opens up the possibility of MR tracking of a wide variety of (stem) cell transplants.

Original languageEnglish (US)
Pages (from-to)1141-1147
Number of pages7
JournalNature Biotechnology
Volume19
Issue number12
DOIs
StatePublished - 2001

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Stem cells
Labeling
Magnetic resonance
Stem Cells
Magnetic Resonance Spectroscopy
Neural Stem Cells
Iron
Galactosidases
Transplants
Nanocomposites
Iron oxides
Endosomes
Neurons
Culture Media
Labels
Magnetic properties
Mesenchymal Stromal Cells
Adsorption
Cells
Nuclear magnetic resonance

ASJC Scopus subject areas

  • Microbiology

Cite this

Bulte, J. W., Douglas, T., Witwer, B., Zhang, S. C., Strable, E., Lewis, B. K., ... Frank, J. A. (2001). Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. Nature Biotechnology, 19(12), 1141-1147. https://doi.org/10.1038/nbt1201-1141

Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. / Bulte, Jeff W; Douglas, Trevor; Witwer, Brian; Zhang, Su Chun; Strable, Erica; Lewis, Bobbi K.; Zywicke, Holly; Miller, Brad; Van Gelderen, Peter; Moskowitz, Bruce M.; Duncan, Ian D.; Frank, Joseph A.

In: Nature Biotechnology, Vol. 19, No. 12, 2001, p. 1141-1147.

Research output: Contribution to journalArticle

Bulte, JW, Douglas, T, Witwer, B, Zhang, SC, Strable, E, Lewis, BK, Zywicke, H, Miller, B, Van Gelderen, P, Moskowitz, BM, Duncan, ID & Frank, JA 2001, 'Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells', Nature Biotechnology, vol. 19, no. 12, pp. 1141-1147. https://doi.org/10.1038/nbt1201-1141
Bulte, Jeff W ; Douglas, Trevor ; Witwer, Brian ; Zhang, Su Chun ; Strable, Erica ; Lewis, Bobbi K. ; Zywicke, Holly ; Miller, Brad ; Van Gelderen, Peter ; Moskowitz, Bruce M. ; Duncan, Ian D. ; Frank, Joseph A. / Magnetodendrimers allow endosomal magnetic labeling and in vivo tracking of stem cells. In: Nature Biotechnology. 2001 ; Vol. 19, No. 12. pp. 1141-1147.
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