In Vivo Visualization and Monitoring of Viable Neural Stem Cells Using Noninvasive Bioluminescence Imaging in the 6-Hydroxydopamine-Induced Mouse Model of Parkinson Disease

Abstract

Transplantation of neural stem cells (NSCs) has been proposed as a treatment for Parkinson disease (PD). The aim of this study was to monitor the viability of transplanted NSCs expressing the enhanced luciferase gene in a mouse model of PD in vivo. The PD animal model was induced by unilateral injection of 6-hydroxydopamine (6-OHDA). The behavioral test using apomorphine-induced rotation and positron emission tomography with [18F]N-(3-fluoropropyl)-2'-carbomethoxy-3'-(4-iodophenyl)nortropane ([18F]FP-CIT) were conducted. HB1.F3 cells transduced with an enhanced firefly luciferase retroviral vector (F3-effLuc cells) were transplanted into the right striatum. In vivo bioluminescence imaging was repeated for 2 weeks. Four weeks after transplantation, [18F]FP-CIT PET and the rotation test were repeated. All 6-OHDA-injected mice showed markedly decreased [18F]FP-CIT uptake in the right striatum. Transplanted F3-effLuc cells were visualized on the right side of the brain in all mice by bioluminescence imaging. The bioluminescence intensity of the transplanted F3-effLuc cells gradually decreased until it was undetectable by 10 days. The behavioral test showed that stem cell transplantation attenuated the motor symptoms of PD. No significant change was found in [18F]FP-CIT imaging after cell transplantation. We successfully established an in vivo bioluminescence imaging system for the detection of transplanted NSCs in a mouse model of PD. NSC transplantation induced behavioral improvement in PD model mice.

In vivo bioluminescence imaging for viable human neural stem cells incorporated within in situ gelatin hydrogels

“…We used the F3-effluc cells that expressed stably the enhanced firefly luciferase (effluc) gene. F3-effluc cells showed more than 85% purity, measured by MACS using anti-CD90.1 microbeads [ 26 ]. After the same number of F3-effluc cell was mixed with the soft GPT 1.8 K or the stiff GPT 5.8 K, initial (day 0) phase contrast images showed a distinct boundary of hardening hydrogel matrix containing an evenly distributed F3-effluc cells.…”

Effects of stem cell therapy on protein profile of parkinsonian rats using an18O‐labeling quantitative proteomic approach

“…(i) Rats sacrificed at different time points cannot be used to evaluate a part of the whole treatment group nor can they reveal the final results of NSC treatment. (ii) It is impossible to evaluate the precise survival duration of transplanted cells . Despite the fact that certain imaging techniques now enable measurement of the viability of grafted NSCs in animal models, each technique has its own limitation.…”

Proposed Motor Scoring System in a Porcine Model of Parkinson’s Disease induced by Chronic Subcutaneous Injection of MPTP

“…The [ 18 F]FP-CIT is a well-established dopamine transporter imaging probe [24] and has been used for imaging dopaminergic neuron degeneration in mouse, rat and monkey PD models induced by MPTP [25, 26, 27, 28]. To the best of our knowledge, this is the first report to show decreased dopaminergic neuron density using [ 18 F]FP-CIT imaging in a MPTP-induced pig model.…”