Abstract
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Several treatments for PD have focused on the management of physical symptoms using dopaminergic agents. However, these treatments induce various adverse effects, including hallucinations and cognitive impairment, owing to non-targeted brain delivery, while alleviating motor symptoms. Furthermore, these therapies are not considered ultimate cures owing to limited brain self-repair and regeneration abilities. In the present study, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASCs) using magnetic nanoparticles in a 6-hydroxydopamine (6-OHDA)-induced PD mouse model. We used the Maestro imaging system and magnetic resonance imaging (MRI) for in vivo tracking after transplantation of magnetic nanoparticle-loaded hASCs to the PD mouse model. The Maestro imaging system revealed strong hASCs signals in the brains of PD model mice. In particular, MRI revealed hASCs distribution in the substantia nigra of hASCs-injected PD mice. Behavioral evaluations, including apomorphine-induced rotation and rotarod performance, were significantly recovered in hASCs-injected 6-OHDA induced PD mice when compared with saline-treated counterparts. Herein, we investigated whether hASCs transplantation using magnetic nanoparticles recovered motor functions through targeted brain distribution in a 6-OHDA induced PD mice. These results indicate that magnetic nanoparticle-based hASCs transplantation could be a potential therapeutic strategy in PD.
Highlights
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) [1]
Baseline behaviors including body weight, apomorphine-induced rotation test, which measures the hypersensitivity of the lesioned striatum, and the rotarod test, used to assess motor coordination, were performed to evaluate the PD mouse model 1 week after 6-OHDA injection (2 days before human adipose-derived stem cells (hASCs) injection) (Figure 1A)
To assess the motor recovery following hASCs transplantation, an apomorphine-induced rotation test and rotarod test were performed at 3 weeks (12 days after hASCs injection) and 6 weeks (33 days after hASCs injection) after 6-OHDA injection (Figure 1A)
Summary
Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra (SN) [1]. Several treatments for PD have focused on the management of physical symptoms using dopaminergic drugs [1,2,3] These treatments cause various adverse effects including hallucinations and cognitive impairment owing to the non-targeted delivery to the brain despite alleviating motor symptoms of PD. These agents are not deemed ultimate cures for the disease itself owing to limited abilities of brain self-repair and regeneration [4]. Stem cell-based regenerative therapy is known to improve neuroprotection and tissue repair ability in neurodegenerative diseases [5,10]. The blood brain barrier (BBB) is still a major limitation for stem cell delivery to the brain [17]
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