Synthesis of SPIO Nanoparticles and the Subsequent Applications in Stem Cell Labeling for Parkinson's Disease

Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons in the midbrain, and the stem cell transplantation method provides a promising strategy for the treatment. In these studies, tracking the biological behaviors of the transplanted cells in vivo is essential for a basic understanding of stem cell function and evaluation of clinical effectiveness. In the present study, we developed a novel ultrasmall superparamagnetic iron oxide nanoparticles coating with the polyacrylic acid (PAA) and methoxypolyethylene glycol amine (PEG) by thermal decomposition method and a two-step modification. The USPIO-PAA/PEG NPs have a uniform diameter of 10.07 ± 0.55 nm and proper absorption peak of the corresponding ligands, as showed by TEM and FTIR. MTT showed that the survival of cells incubated with USPIO-PAA/PEG NPs remained above 96%. The synthesized USPIO-PAA/PEG had a good relaxation rate of 84.65 s^-1 Mm^-1, indicating that they could be efficiently uptake and traced by MRI. Furthermore, the primary human adipose-derived stem cells (HADSCs) were characterized, labeled with USPIO-PAA/PEG and transplanted into the striatum of 6-hydroxydopamine (6-OHDA)-induced PD rat models. The labeled cells could be traced by MRI for up to 3 weeks after the transplantation surgery; moreover, transplantation with the labeled HADSCs significantly attenuated apomorphine-induced rotations in PD models and increased the number of the dopaminergic neurons in the substania nigra. Overall, the development of USPIO-PAA/PEG NPs provides a promising tool for in vivo tracing technique of cell therapy and identifies a novel strategy to track stem cells with therapeutic potential in PD.