Abstract 5824: Monitoring of Transplanted Endothelial Progenitor Cells after Cell Enhancement Strategy by PET
Background: Stem cell transplantation is promising therapy for myocardial injury, but there is a need to improve engraftment and survival of the cells. VEGF and statins have been suggested to enhance survival, proliferation and function of human endothelial progenitor cells (EPC). We investigated whether reporter gene PET imaging can be used to monitor effects of these survival enhancement strategies on survival of transplanted EPC in the rat heart.
Methods: Nude rats received a intramyocardial injection of 4 million human EPC transduced with the sodium/iodide symporter (NIS) gene for reporter gene imaging. I-124 uptake signal via the NIS expressing on the EPC was imaged after intra venous administration of I-124 (0.7mCi) with a small animal PET scanner on day 1 and 3 and with autoradiography on day 3. Presence of EPC was confirmed by immunohistochemistry with human CD31 antibodies. Control group (n= 5) received EPC only transduced with the NIS reporter gene. Pretreatment groups received
oral atorvastatin (10mg/kg/day) (n= 4),
EPC that were transduced with both VEGF and the NIS reporter gene (n= 5) or
both atorvastatin and VEGF pretreatments (n= 5).
Results: PET imaging successfully visualized graft EPC as focal I-124 accumulation at the site of cell injection. The amount of tracer accumulation assessed by PET (% of injected dose) was significantly higher in the atorvastatin+VEGF pretreatment than in the control group (0.097± 0.015 vs. 0.058± 0.01 on day1 and 0.059± 0.009 vs. 0.037± 0.0012 on day3). Autoradiography consisted with the in vivo imaging signal with higher I-124 uptake ratio in the atorvastatin+VEGF (10± 4.8) than in atorvastatin (4.0± 1.5), VEGF (5.2± 1.3) and the control group (3.3± 0.9) on day3. Number of surviving cells assessed by CD31 immunohistochemistry was significantly correlated with the I-124 uptake assessed by autoradiography (r = 0.87, p< 0.001).
Conclusion: The graft EPCs viability augmented by a combination of VEGF and statin was successfully monitored by I-124 signal of reporter gene PET imaging. Notably, the I-124 signal correlated well with the number of surviving cells counted by CD31 immunohistochemical analysis. This imaging assay may be helpful to optimize the cell-enhancement strategies in stem cell therapy.