Abstract 1106: In Vivo Molecular Imaging for Cardiac Regeneration
Introduction We have showed that the transplanted human peripheral blood CD34+cells can transform into smooth muscle, endothelial, and myocardial cells in infarcted hearts in mice. However, the fate of the transplanted cells in vivo is unknown.
Hypothesis Molecular imaging is of substantial value for non-invasively tracking the fate of transplanted stem cells and for developing stem cell transplantation toward a clinically accepted therapy.
Objectives To develop and validate molecular imaging techniques for reliably tracking the fate of transplanted stem cells in ischemic hearts in vivo and to follow the tempo-spatial dynamics of their transformation and function.
Methods Using SCID mice transplanted with the CD34+cells after myocardial infarction as a model, the CD34+cells were transduced with 6 lentivectors bearing a fusion reporter gene driven by 6 different promoters. The reporter protein consists of herpes simplex virus thymidine kinase, green fluorescence protein, and luciferase, allowing us to monitor in vivo the fate of transplanted cells with bioluminescence imaging (BLI) and positron emission tomography (PET). In order to assess cardiac function, the mice were scanned with a 7.0-T MRI.
Results The virus containing human ubiquitin promoter produced stable transduction efficiency 30%. Thereafter, 106 transduced CD34+cells were injected into peri-infarct area per mouse heart. At day 7, the BLI signals in hearts were 1.4 ± 0.12x105 photons(p)/s/cm2/sr (n=6). At day 14, the PET signals were 0.05 ± 0.001 injection dose (ID) %/g. Both signals increased progressively to week 4, then remained in plateaus of 1.8 ± 0.15x105 p/s/cm2/sr and 1.38 ± 0.002 ID%/g, respectively until week 6, thereafter declining gradually, but were still as high as 9 ± 0.11x104 p/s/cm2/sr and 0.92 ± 0.001 ID%/g at week 16, indicating the transplanted CD34+cells survive and function in the host. Co-register MRI/PET showed the concordance of anatomic and functional consequences after the transplantation of the CD34+cells.
Conclusion Our results demonstrate the feasibility of using molecular imaging to reliably track human CD34+cell transplanted into infarcted hearts in mice, thus identifying PET/MRI imaging as a means to trace stem cell transplants in injured hearts.