Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease, which is clinically and pathologically characterized by motor dysfunction and the loss of dopaminergic neurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by researchers; however, no adequate treatment strategy has been established. The results of studies so far have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is a progressively deteriorating neurodegenerative disease that requires long-term treatment, and this has been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human adipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal model of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice, hASCs were administered on the tail vein six times at two-week intervals. After the last injection of hASCs, motor function significantly improved. The number of dopaminergic neurons present in the nigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of hASC restored altered dopamine transporter expression and increased neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the striatum. Overall, this study suggests that repeated intravenous transplantation of hASC may exert therapeutic effects on PD by restoring BDNF and GDNF expressions, protecting dopaminergic neurons, and maintaining the nigrostriatal pathway.
Highlights
Parkinson’s disease (PD) is a gradually progressive neurodegenerative disease characterized by motor function decline
We discovered that intravenous injections of human adipose-derived stem cells (hASC) in MPTP-induced PD model mice alleviated motor function by restoring the levels of brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) expression in dopaminergic terminals
Animal models primarily used in PD studies include genetically modified models and toxin (e.g., 6-OHDA and MPTP)-induced models
Summary
Parkinson’s disease (PD) is a gradually progressive neurodegenerative disease characterized by motor function decline. The primary causes of PD are age, genetic factors, and environmental factors; the exact mechanism underlying its onset is poorly understood. The risk factors for PD are age, heredity, sex, and exposure to neurotoxins. PD symptoms include slowed movement (bradykinesia), rigid muscles, impaired posture and balance, and shaking [1,2,3]. These motor disorders are influenced by the loss of dopaminergic neurons projected from the substantia nigra (SN) to the striatum (ST) [4]. PD treatments include levodopa (L-DOPA), a precursor of dopamine (DA); catechol-O-methyltransferase (COMT) and monoamine oxidase-B (MAO-B) inhibitors to prevent
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