Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents

Joseph A. Frank, Brad R. Miller, Ali Syed Arbab, Holly A. Zywicke, E. Kay Jordan, Bobbi K. Lewis, L. Henry Bryant, Jeff W.M. Bulte

Research output: Contribution to journalArticle

582 Citations (Scopus)

Abstract

PURPOSE: To label mammalian and stem cells by combining commercially available transfection agents (TAs) with superparamagnetic iron oxide (SPIO) magnetic resonance (MR) imaging contrast agents. MATERIALS AND METHODS: Three TAs were incubated with ferumoxides and MION-46L in cell culture medium at various concentrations. Human mesenchymal stem cells, mouse lymphocytes, rat oligodendrocyte progenitor CG-4 cells, and human cervical carcinoma cells were incubated 2-48 hours with 25 μg of iron per milliliter of combined TAs and SPIO. Cellular labeling was evaluated with T2 relaxometry, MR imaging of labeled cell suspensions, and Prussian blue staining for iron assessment. Proliferation and viability of mesenchymal stem cells and human cervical carcinoma cells labeled with a combination of TAs and ferumoxides were evaluated. RESULTS: When ferumoxides-TA or MION-46L-TA was used, intracytoplasmic particles stained with Prussian blue stain were detected for all cell lines with a labeling efficiency of nearly 100%. Limited or no uptake was observed for cells incubated with ferumoxides or MION-46L alone. For TA-SPIO-labeled cells, MR images and relaxometry findings showed a 50%-90% decrease in signal intensity and a more than 40-fold increase in T2s. Cell viability varied from 103.7% ± 9 to 123.0% ± 9 compared with control cell viability at 9 days, and cell proliferation was not affected by endosomal incorporation of SPIO nanoparticles. Iron concentrations varied with ferumoxides-TA combinations and cells with a maximum of 30.1 pg ± 3.7 of iron per cell for labeled mesenchymal stem cells. CONCLUSION: Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.

Original languageEnglish (US)
Pages (from-to)480-487
Number of pages8
JournalRadiology
Volume228
Issue number2
DOIs
StatePublished - Aug 1 2003

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Transfection
Stem Cells
Iron
Mesenchymal Stromal Cells
Magnetic Resonance Imaging
Cell Survival
Carcinoma
ferric oxide
Oligodendroglia
Nanoparticles
Contrast Media
Culture Media
ferumoxides
Suspensions
Coloring Agents
Magnetic Resonance Spectroscopy
Cell Culture Techniques
Cell Proliferation
Lymphocytes
Staining and Labeling

Keywords

  • Cell labeling
  • Experimental study
  • Iron
  • Magnetic resonance (MR), experimental studies
  • Stem cells

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. / Frank, Joseph A.; Miller, Brad R.; Arbab, Ali Syed; Zywicke, Holly A.; Jordan, E. Kay; Lewis, Bobbi K.; Bryant, L. Henry; Bulte, Jeff W.M.

In: Radiology, Vol. 228, No. 2, 01.08.2003, p. 480-487.

Research output: Contribution to journalArticle

Frank, JA, Miller, BR, Arbab, AS, Zywicke, HA, Jordan, EK, Lewis, BK, Bryant, LH & Bulte, JWM 2003, 'Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents', Radiology, vol. 228, no. 2, pp. 480-487. https://doi.org/10.1148/radiol.2281020638
Frank, Joseph A. ; Miller, Brad R. ; Arbab, Ali Syed ; Zywicke, Holly A. ; Jordan, E. Kay ; Lewis, Bobbi K. ; Bryant, L. Henry ; Bulte, Jeff W.M. / Clinically applicable labeling of mammalian and stem cells by combining superparamagnetic iron oxides and transfection agents. In: Radiology. 2003 ; Vol. 228, No. 2. pp. 480-487.
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abstract = "PURPOSE: To label mammalian and stem cells by combining commercially available transfection agents (TAs) with superparamagnetic iron oxide (SPIO) magnetic resonance (MR) imaging contrast agents. MATERIALS AND METHODS: Three TAs were incubated with ferumoxides and MION-46L in cell culture medium at various concentrations. Human mesenchymal stem cells, mouse lymphocytes, rat oligodendrocyte progenitor CG-4 cells, and human cervical carcinoma cells were incubated 2-48 hours with 25 μg of iron per milliliter of combined TAs and SPIO. Cellular labeling was evaluated with T2 relaxometry, MR imaging of labeled cell suspensions, and Prussian blue staining for iron assessment. Proliferation and viability of mesenchymal stem cells and human cervical carcinoma cells labeled with a combination of TAs and ferumoxides were evaluated. RESULTS: When ferumoxides-TA or MION-46L-TA was used, intracytoplasmic particles stained with Prussian blue stain were detected for all cell lines with a labeling efficiency of nearly 100{\%}. Limited or no uptake was observed for cells incubated with ferumoxides or MION-46L alone. For TA-SPIO-labeled cells, MR images and relaxometry findings showed a 50{\%}-90{\%} decrease in signal intensity and a more than 40-fold increase in T2s. Cell viability varied from 103.7{\%} ± 9 to 123.0{\%} ± 9 compared with control cell viability at 9 days, and cell proliferation was not affected by endosomal incorporation of SPIO nanoparticles. Iron concentrations varied with ferumoxides-TA combinations and cells with a maximum of 30.1 pg ± 3.7 of iron per cell for labeled mesenchymal stem cells. CONCLUSION: Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.",
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AU - Frank, Joseph A.

AU - Miller, Brad R.

AU - Arbab, Ali Syed

AU - Zywicke, Holly A.

AU - Jordan, E. Kay

AU - Lewis, Bobbi K.

AU - Bryant, L. Henry

AU - Bulte, Jeff W.M.

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N2 - PURPOSE: To label mammalian and stem cells by combining commercially available transfection agents (TAs) with superparamagnetic iron oxide (SPIO) magnetic resonance (MR) imaging contrast agents. MATERIALS AND METHODS: Three TAs were incubated with ferumoxides and MION-46L in cell culture medium at various concentrations. Human mesenchymal stem cells, mouse lymphocytes, rat oligodendrocyte progenitor CG-4 cells, and human cervical carcinoma cells were incubated 2-48 hours with 25 μg of iron per milliliter of combined TAs and SPIO. Cellular labeling was evaluated with T2 relaxometry, MR imaging of labeled cell suspensions, and Prussian blue staining for iron assessment. Proliferation and viability of mesenchymal stem cells and human cervical carcinoma cells labeled with a combination of TAs and ferumoxides were evaluated. RESULTS: When ferumoxides-TA or MION-46L-TA was used, intracytoplasmic particles stained with Prussian blue stain were detected for all cell lines with a labeling efficiency of nearly 100%. Limited or no uptake was observed for cells incubated with ferumoxides or MION-46L alone. For TA-SPIO-labeled cells, MR images and relaxometry findings showed a 50%-90% decrease in signal intensity and a more than 40-fold increase in T2s. Cell viability varied from 103.7% ± 9 to 123.0% ± 9 compared with control cell viability at 9 days, and cell proliferation was not affected by endosomal incorporation of SPIO nanoparticles. Iron concentrations varied with ferumoxides-TA combinations and cells with a maximum of 30.1 pg ± 3.7 of iron per cell for labeled mesenchymal stem cells. CONCLUSION: Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.

AB - PURPOSE: To label mammalian and stem cells by combining commercially available transfection agents (TAs) with superparamagnetic iron oxide (SPIO) magnetic resonance (MR) imaging contrast agents. MATERIALS AND METHODS: Three TAs were incubated with ferumoxides and MION-46L in cell culture medium at various concentrations. Human mesenchymal stem cells, mouse lymphocytes, rat oligodendrocyte progenitor CG-4 cells, and human cervical carcinoma cells were incubated 2-48 hours with 25 μg of iron per milliliter of combined TAs and SPIO. Cellular labeling was evaluated with T2 relaxometry, MR imaging of labeled cell suspensions, and Prussian blue staining for iron assessment. Proliferation and viability of mesenchymal stem cells and human cervical carcinoma cells labeled with a combination of TAs and ferumoxides were evaluated. RESULTS: When ferumoxides-TA or MION-46L-TA was used, intracytoplasmic particles stained with Prussian blue stain were detected for all cell lines with a labeling efficiency of nearly 100%. Limited or no uptake was observed for cells incubated with ferumoxides or MION-46L alone. For TA-SPIO-labeled cells, MR images and relaxometry findings showed a 50%-90% decrease in signal intensity and a more than 40-fold increase in T2s. Cell viability varied from 103.7% ± 9 to 123.0% ± 9 compared with control cell viability at 9 days, and cell proliferation was not affected by endosomal incorporation of SPIO nanoparticles. Iron concentrations varied with ferumoxides-TA combinations and cells with a maximum of 30.1 pg ± 3.7 of iron per cell for labeled mesenchymal stem cells. CONCLUSION: Magnetic labeling of mammalian cells with use of ferumoxides and TAs is possible and may enable cellular MR imaging and tracking in experimental and clinical settings.

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KW - Experimental study

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KW - Magnetic resonance (MR), experimental studies

KW - Stem cells

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