Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival

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

doi:10.1007/s11307-006-0038-3

Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival

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

Cardiovascular Medicine

Research output: Contribution to journal › Article › peer-review

13 Scopus citations

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.

Original language	English (US)
Pages (from-to)	163-170
Number of pages	8
Journal	Molecular Imaging and Biology
Volume	8
Issue number	3
DOIs	https://doi.org/10.1007/s11307-006-0038-3
State	Published - May 2006

Keywords

Cell transplant
Cyclosporine
Molecular imaging
Mycophenolate
Tacrolimus

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

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10.1007/s11307-006-0038-3

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title = "Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival",

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.",

keywords = "Cell transplant, Cyclosporine, Molecular imaging, Mycophenolate, Tacrolimus",

author = "Olivier Gheysens and Shuan Lin and Feng Cao and Dongxu Wang and Chen, {Ian Y.} and Martin Rodriguez-Porcel and Min, {Jung J.} and Gambhir, {Sanjiv S.} and Wu, {Joseph C.}",

note = "Funding Information: 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 BelgiumVFlanders (O.G.). O. Gheysens and S. Lin contributed equally to this work.",

year = "2006",

month = may,

doi = "10.1007/s11307-006-0038-3",

language = "English (US)",

volume = "8",

pages = "163--170",

journal = "Molecular Imaging and Biology",

issn = "1536-1632",

publisher = "Springer New York",

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TY - JOUR

T1 - Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival

AU - Gheysens, Olivier

AU - Lin, Shuan

AU - Cao, Feng

AU - Wang, Dongxu

AU - Chen, Ian Y.

AU - Rodriguez-Porcel, Martin

AU - Min, Jung J.

AU - Gambhir, Sanjiv S.

AU - Wu, Joseph C.

N1 - Funding Information: 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 BelgiumVFlanders (O.G.). O. Gheysens and S. Lin contributed equally to this work.

PY - 2006/5

Y1 - 2006/5

N2 - 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.

AB - 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.

KW - Cell transplant

KW - Cyclosporine

KW - Molecular imaging

KW - Mycophenolate

KW - Tacrolimus

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SN - 1536-1632

VL - 8

SP - 163

EP - 170

JO - Molecular Imaging and Biology

JF - Molecular Imaging and Biology

IS - 3

ER -

Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival

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