In vivo visualization of viable neural stem cells expressing high sensitive optical imaging reporters in mouse model of Parkinson’s disease

Objectives Neural stem cells (NSC) have been proposed to be potential sources to treat Parkinson’s disease (PD). Evaluating the characteristics of transplanted stem cells using optical imaging tools non-invasively can help us to understand fate of grafted stem cells in PD model. Here, we successfully monitored in vivo viability of transplanted neural stem cells expressing enhanced luciferase gene in PD mouse model, and observed functional recovery after transplantation.

Methods 6-OHDA was streotactically injected into the right striatum to induce PD in C57BL/6 mice (n=6). Behavioral test with apomorphine induced rotation test and [18F]FP-CIT imaging were done to confirm the establishment of PD. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc) were transplanted in the right striatum. In vivo bioluminescence imaging was serially followed up. 4 weeks after transplantation, [18F]FP-CIT and behavioral test were followed up.

Results By DAT imaging and behavioral test, all mice were proved to develop PD; markedly decreased right striatal uptake on [18F]FP-CIT imaging, significant contralateral limb motor impairments. Transplanted F3-effLuc cells were easily visualized in the right side of the brain in all mice by bioluminescence imaging. The bioluminescence activity of the transplanted F3-effLuc cells was gradually decreased and then disappeared on 10 day. Follow up behavioral test revealed that stem cell transplantation attenuate the motor symptom. No significant change was found in DAT imaging after cell transplantation.

Conclusions We established in vivo bioluminescence imaging system of transplanted NSCs in PD mouse model, which enabled to longitudinally monitor the survival of the NSCs without sacrificing the animals. PD model showed behavioral improvement by NSC transplantation