Abstract
Persephin (PSPN) is one of the neurotrophic factors of the glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) which have been found to promote the survival of specific populations of neurons. The aim of this study was to assess the potential therapeutic function of gene-modified mesenchymal stem cells (MSCs)-Lv-PSPN-MSCs in 6-OHDA-induced Parkinson’s disease (PD) rats models. Here, we worked on the isolation, purification, identification and amplification of MSCs in vitro. The expression analysis revealed that several of the neural marker proteins like nestin, GFAP and S100 were expressed by rat MSCs. MES23.5 cells co-cultured with Lv-PSPN-MSCs showed less 6-OHDA induced cell death than control cells in vitro. When Lv-PSPN-MSCs were injected into the striatum of PD rats, we observed the survival rate, migration, differentiation and the behavior change of PD rats. We found that Lv-PSPN-MSCs showed higher survival rate in rat brain compared with Lv-null-MSCs. Rotational behavior showed that rats receiving Lv-PSPN-MSCs showed the most significant improvement compared with those in other groups. HPLC results showed the content of DA in striatum of rats which received Lv-PSPN-MSCs was highest compared with those in other groups. In conclusion, our results suggest that transplantation of Lv-PSPN-MSCs can lead to remarkable therapeutic effects in PD rats.
Highlights
Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world
In order to observe the effect of Lv-PSPN-mesenchymal stem cells (MSCs) on cell apoptosis, we performed FACS analysis on MES23.5 cells that were co-cultured with Lv-null-MSCs or Lv-PSPN-MSCs respectively after 6OHDA (100 mM) treatment
Lv-PSPN-MSCs could be detected within the striatum (Fig. 6 F), which was used as the target structure for the injection, while others had already attached either to the contralateral striatum (Fig. 6 G), periventricular regions (Fig. 6 H–I) and cerebral cortex (Fig. 6 J)
Summary
Parkinson’s disease (PD) is the second most common neurodegenerative disease in the world. It is characterized by the progressive degeneration of dopaminergic neurons in locus ceruleus and substantia nigra (SN), which leads to the reduction of dopamine (DA) levels in striatum [1]. The progressive loss of nigral dopaminergic neurons results in a series of clinical symptoms, including hypokinesia, static tremor, muscle rigidity, and abnormal posture and pace [2]. Drug therapy and surgical treatment can relieve the symptoms, they cannot prevent the progression of the disease and fundamentally cure PD, because the loss of neurons cannot be restored. Cell transplantation is a therapy to replace the loss of neurons in SN, the efficacy is apparent but not lasting. The present study focuses on how to develop more effectively long-term therapies for PD
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