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Noninvasive Evaluation of Immunosuppressive Drug Efficacy on Acute Donor Cell Survival

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Abstract

Purpose

The therapeutic benefits of cell transplantation may depend on the survival of sufficient numbers of grafted cells. We evaluate four potent immunosuppressive medications aimed at preventing acute donor cell death.

Procedures and Results

Embryonic rat H9c2 myoblasts were stably transduced to express firefly luciferase reporter gene (H9c2-Fluc). H9c2-Fluc cells (3 × 106) were injected into thigh muscles of Sprague–Dawley rats (N = 30) treated with cyclosporine, dexamethasone, mycophenolate mofetil, tacrolimus, or saline from day −3 to day +14. Longitudinal optical bioluminescence imaging was performed over two weeks. Fluc activity was 40.0 ± 12.1% (dexamethasone), 30.5 ± 12.5% (tacrolimus), and 21.5 ± 3.5% (mycophenolate) vs. 12.0 ± 5.0% (control) and 8.3 ± 5.0% (cyclosporine) at day 4 (P < 0.05). However, by day 14, cell signals had decreased drastically to <10% for all groups despite drug therapy.

Conclusion

This study demonstrates the ability of optical molecular imaging for tracking cell survival noninvasively and raises important questions with regard to the overall efficacy of immunosuppressives for prolonging transplanted cell survival.

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Acknowledgments

This work was supported in part by grants from the ASNC, GSK, AHA, and NHLBI (J.C.W.); NCI ICMIC-P50, NHLBI R01 HL078632, NCI SAIRP (S.S.G.); and Fund for Scientific Research Belgium—Flanders (O.G.). O. Gheysens and S. Lin contributed equally to this work.

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Authors and Affiliations

  1. Department of Radiology and Bio-X Program, Stanford University, Palo Alto, CA, USA

    Olivier Gheysens, Shuan Lin, Feng Cao, Dongxu Wang, Ian Y. Chen, Martin Rodriguez-Porcel, Jung J. Min, Sanjiv S. Gambhir & Joseph C. Wu

  2. Department of Bioengineering, Stanford University, Palo Alto, CA, USA

    Sanjiv S. Gambhir

  3. Department of Medicine, Division of Cardiology, Stanford University, Palo Alto, CA, USA

    Joseph C. Wu

  4. Stanford School of Medicine, Edwards Building, R354, Stanford, CA, 94305-5344, USA

    Joseph C. Wu

Authors
  1. Olivier Gheysens
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  2. Shuan Lin
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  3. Feng Cao
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  4. Dongxu Wang
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  5. Ian Y. Chen
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  6. Martin Rodriguez-Porcel
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  7. Jung J. Min
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  8. Sanjiv S. Gambhir
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  9. Joseph C. Wu
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Corresponding author

Correspondence to Joseph C. Wu.

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Gheysens, O., Lin, S., Cao, F. et al. Noninvasive Evaluation of Immunosuppressive Drug Efficacy on Acute Donor Cell Survival. Mol Imaging Biol 8, 163–170 (2006). https://doi.org/10.1007/s11307-006-0038-3

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  • DOI: https://doi.org/10.1007/s11307-006-0038-3

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