Noninvasive evaluation of immunosuppressive drug efficacy on acute donor cell survival.
OBJECTIVE
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.


RESULTS
Embryonic rat H9c2 myoblasts were stably transduced to express firefly luciferase reporter gene (H9c2-Fluc). H9c2-Fluc cells (3x10(6)) 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.


CONCLUSIONS
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.
Gheysens
Olivier
O
Department of Radiology and Bio-X Program, Stanford University, Palo Alto, CA, USA.
Lin
Shuan
S
Cao
Feng
F
Wang
Dongxu
D
Chen
Ian Y
IY
Rodriguez-Porcel
Martin
M
Min
Jung J
JJ
Gambhir
Sanjiv S
SS
Wu
Joseph C
JC
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008137:Longitudinal Studies; D049449:Luminescence; D009173:Mycophenolic Acid / Q000494:pharmacology; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects* / Q000637:transplantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology; D014162:Transfection
D007166:Immunosuppressive Agents; D003907:Dexamethasone; D016572:Cyclosporine; D009173:Mycophenolic Acid; D016559:Tacrolimus