Molecular Imaging and Biology

, Volume 13, Issue 5, pp 911–922 | Cite as

In Situ Labeling and Magnetic Resonance Imaging of Transplanted Human Hepatic Stem Cells

  • Randall McClelland
  • Eliane Wauthier
  • Tommi Tallheden
  • Lola M. Reid
  • Edward Hsu
Research Article

Abstract

Purpose

The purpose is to address the problem in magnetic resonance imaging (MRI) of contrast agent dilution.

Procedures

In situ magnetic labeling of cells and MRI were used to assess distribution and growth of human hepatic stem cells (hHpSCs) transplanted into severe combined immunodeficiency (SCID)/non-obese diabetic (NOD) mice. It was done with commercially available magnetic microbeads coupled to an antibody to a surface antigen, epithelial cell adhesion molecule (EpCAM), uniquely expressed in the liver by hepatic progenitors.

Results

We validated the microbead connection to cells and related MRI data to optical microscopy observations in order to develop a means to quantitatively estimate cell numbers in the aggregates detected. Cell counts of hHpSCs at different times post-transplantation revealed quantifiable evidence of cell engraftment and expansion.

Conclusions

This magnetic labeling methodology can be used with any antibody coupled to a magnetic particle to target any surface antigen that distinguishes transplanted cells from host cells, thus facilitating studies that define methods and strategies for clinical cell therapy programs.

Key words

Magnetic resonance imaging (MRI) Cell labeling and tracking Human hepatic stem cells Cell therapies EpCAM 

Abbreviations

AFP

α-Fetoprotein

ALB

Albumin

CK

Cytokeratin

EpCAM

Epithelial cell adhesion molecule

HDM

Hormonally defined medium

hHB

Human hepatoblast

hHpSC

Human hepatic stem cell

KM

Kubota’s medium

MACS

Magnetically activated cell sorting

MRI

Magnetic resonance imaging

Notes

Acknowledgements

Technical and administrative support was provided by Lucendia English, Victoria Morgan, and Dr. Claire Barbier. The microscopy was done in the Michael Hooker Confocal Microscope Facility at UNC (Dr. Michael Chua, director) and the electron microscopy in the Microscope Facility (Dr. Robert Bagnell, director). We thank Dr. Sharon Lubkin for a critical evaluation of the paper and Dr. Claire Barbier for editing the figures.

This work was funded primarily by a US Department of Energy (DOE) grant (DE-FG02-02ER-63477). It derived also from grants from the North Carolina Biotechnology Center, Vesta Therapeutics (Bethesda, MD), the National Institutes of Health (NIH; AA014243 and IP30-DK065933), the National Institute of Diabetes and Digestive and Kidney Diseases (DK34987), and the National Cancer Institute (CA016086). All of the imaging was done in the Duke Center for In Vivo Microscopy (Dr. G.A. Johnson, director), an NIH/National Center for Research Resources Biomedical Technology Resource Center (P41 RR005959) and Small Animal Imaging Resource Program (U24 CA092656).

Conflict of Interest

None

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Copyright information

© Academy of Molecular Imaging and Society for Molecular Imaging 2010

Authors and Affiliations

  • Randall McClelland
    • 1
    • 7
  • Eliane Wauthier
    • 1
  • Tommi Tallheden
    • 1
    • 8
  • Lola M. Reid
    • 1
    • 2
    • 3
    • 5
  • Edward Hsu
    • 4
    • 6
  1. 1.Department of Cell and Molecular PhysiologyUNC School of MedicineChapel HillUSA
  2. 2.Department of Biomedical EngineeringUNC School of MedicineChapel HillUSA
  3. 3.Program in Molecular Biology and BiotechnologyUNC School of MedicineChapel HillUSA
  4. 4.Department of Biomedical EngineeringDuke UniversityDurhamUSA
  5. 5.Room 34, UNC School of MedicineChapel HillUSA
  6. 6.Department of BioengineeringUniversity of UtahSalt Lake CityUSA
  7. 7.SciKonResearch Triangle ParkUSA
  8. 8.Laboratoriet för Klinisk kemi och TransfusionsmedicinSkeneSweden

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